Nonclassical MHC-I Molecules: Emerging Therapeutic Targets in Next-Generation Immunotherapy

Abstract

Immunotherapies have transformed the treatment of cancers and infectious diseases by harnessing the precision and adaptability of the immune system. Central to these advances is the major histocompatibility complex (MHC) system, with classical MHC-I molecules well documented for their role in immune surveillance. MHC-dependent therapies, including immune checkpoint blockade (ICB), T cell receptor (TCR)-engineered therapies, and cancer vaccines, have shown substantial clinical promise. However, their broader efficacy is hindered by the extreme polymorphism of classical MHC-I molecules, susceptibility to immune evasion, and frequent downregulation in many disease settings. In contrast, nonclassical MHC-I molecules, including HLA-E, HLA-F, HLA-G, CD1, and MR1, offer alternative therapeutic opportunities. Shaped by strong evolutionary conservation, these molecules exhibit limited polymorphism, specialized antigen repertoires, distinct trafficking behaviors, and the capability to engage both innate and adaptive immune cells. In this review, we synthesize current knowledge of the structural biology, antigen presentation pathways, receptor interactions, and immunoregulatory functions of nonclassical MHC-I molecules. We further highlight emerging therapeutic strategies, including immune checkpoint modulation, cargo-based ligands, conformation-specific biologics, vaccines, and cellular therapies, while critically evaluating translational challenges. By linking specialized structural and functional features to therapeutic design, this review provides a unified framework for exploiting nonclassical MHC-I molecules as next-generation targets in immunotherapy.

Keywords

antigen presentation / immunotherapy / immune modulation / innate–adaptive crosstalk / nonclassical MHC-I molecules

References

[1] M. F. Flajnik and M. Kasahara, “Origin and Evolution of the Adaptive Immune System: Genetic Events and Selective Pressures,” Nature Reviews Genetics 11, no. 1 (2010): 47–59.

[2] J. Radwan, W. Babik, J. Kaufman, et al., “Advances in the Evolutionary Understanding of MHC Polymorphism,” Trends in Genetics 36, no. 4 (2020): 298–311.

[3] S. Medhasi and N. Chantratita, “Human Leukocyte Antigen (HLA) System: Genetics and Association With Bacterial and Viral Infections,” Journal of Immunology Research 2022 (2022): 9710376.

[4] P. Lin, Y. Lin, Z. Mai, et al., “Targeting Cancer With Precision: Strategical Insights Into TCR-engineered T Cell Therapies,” Theranostics 15, no. 1 (2025): 300–323.

[5] A. N. Antoniou and S. J. Powis, “Pathogen Evasion Strategies for the Major Histocompatibility Complex Class I Assembly Pathway,” Immunology 124 (2008): 1–12.

[6] C. Graham, A. Jozwik, A. Pepper, et al., “Allogeneic CAR-T Cells: More Than Ease of Access?,” Cells 7, no. 10 (2018): 155.

[7] G. Ogg, V. Cerundolo, and A. J. McMichael, “Capturing the Antigen Landscape: HLA-E, CD1 and MR1,” Current Opinion in Immunology 59 (2019): 121–129.

[8] P. A. Gorer, S. Lyman, G. D. Snell, et al., “Studies on the Genetic and Antigenic Basis of Tumour Transplantation: Linkage Between a Histocompatibility Gene and “Fused” in Mice,” Proceedings of the Royal Society B 135 (1948): 499–505.

[9] H. O. McDevitt and M. Sela, “Genetic Control of the Antibody Response. II. Further Analysis of the Specificity of Determinant-specific Control, and Genetic Analysis of the Response to (H, G)-A–L in CBA and C57 Mice,” Journal of Experimental Medicine 126, no. 5 (1967): 969–978.

[10] F. Lilly, E. A. Boyse, and L. J. Old, “Genetic Basis of Susceptibility to Viral Leukaemogenesis,” Lancet 2, no. 7371 (1964): 1207–1209.

[11] R. M. Zinkernagel and P. C. Doherty, “Restriction of in Vitro T Cell-mediated Cytotoxicity in Lymphocytic Choriomeningitis Within a Syngeneic or Semiallogeneic System,” Nature 248, no. 5450 (1974): 701–702.

[12] E. Goulmy, A. Termijtelen, B. A. Bradley, et al., “Y-antigen Killing by T Cells of Women Is Restricted by HLA,” Nature 266, no. 5602 (1977): 544–545.

[13] R. M. Zinkernagel and P. C. Doherty, “Immunological Surveillance Against Altered Self Components by Sensitised T Lymphocytes in Lymphocytic Choriomeningitis,” Nature 251, no. 5475 (1974): 547–548.

[14] A. R. Townsend, J. Rothbard, F. M. Gotch, et al., “The Epitopes of Influenza Nucleoprotein Recognized by Cytotoxic T Lymphocytes Can be Defined With Short Synthetic Peptides,” Cell 44, no. 6 (1986): 959–968.

[15] B. P. Babbitt, P. M. Allen, G. Matsueda, et al., “Binding of Immunogenic Peptides to Ia Histocompatibility Molecules,” Nature 317, no. 6035 (1985): 359–361.

[16] P. M. Allen, G. R. Matsueda, E. Haber, et al., “Specificity of the T Cell Receptor: Two Different Determinants Are Generated by the Same Peptide and the I-Ak Molecule,” Journal of Immunology 135, no. 1 (1985): 368–373.

[17] P. J. Bjorkman, M. A. Saper, B. Samraoui, et al., “HLA-A2,” Nature 329, no. 6139 (1987): 506–512.

[18] J. K. Kulski, S. Suzuki, and T. Shiina, “Human Leukocyte Antigen Super-locus: Nexus of Genomic Supergenes, SNPs, Indels, Transcripts, and Haplotypes,” Human Genome Variation 9, no. 1 (2022): 49.

[19] T. Shiina, K. Hosomichi, H. Inoko, et al., “The HLA Genomic Loci Map: Expression, Interaction, Diversity and Disease,” Journal of Human Genetics 54, no. 1 (2009): 15–39.

[20] E. D. Mellins and L. J. Stern, “HLA-DM and HLA-DO, Key Regulators of MHC-II Processing and Presentation,” Current Opinion in Immunology 26 (2014): 115–122.

[21] C. M. Milner and R. D. Campbell, “Genetic Organization of the human MHC Class III Region,” Frontiers in Bioscience 6 (2001): D914–D926.

[22] D. J. Barker, G. Maccari, X. Georgiou, et al., “The IPD-IMGT/HLA Database,” Nucleic Acids Research 51, no. D1 (2023): D1053–D1060.

[23] J. Trowsdale and J. C. Knight, “Major Histocompatibility Complex Genomics and human Disease,” Annual Review of Genomics and Human Genetics 14 (2013): 301–323.

[24] Y. Kawashima, K. Pfafferott, J. Frater, et al., “Adaptation of HIV-1 to human Leukocyte Antigen Class I,” Nature 458, no. 7238 (2009): 641–645.

[25] M. H. Kuniholm, A. Kovacs, X. Gao, et al., “Specific human Leukocyte Antigen Class I and II Alleles Associated With hepatitis C Virus Viremia,” Hepatology 51, no. 5 (2010): 1514–1522.

[26] J. M. Francis, D. Leistritz-Edwards, A. Dunn, et al., “Allelic Variation in Class I HLA Determines CD8(+) T Cell Repertoire Shape and Cross-reactive Memory Responses to SARS-CoV-2,” Science Immunology 7, no. 67 (2022): eabk3070.

[27] L. Y. Chihab, R. Kuan, E. J. Phillips, et al., “Expression of Specific HLA Class II Alleles Is Associated With an Increased Risk for Active Tuberculosis and a Distinct Gene Expression Profile,” HLA 101, no. 2 (2023): 124–137.

[28] K. Ishigaki, K. A. Lagattuta, Y. Luo, et al., “HLA Autoimmune Risk Alleles Restrict the Hypervariable Region of T Cell Receptors,” Nature Genetics 54, no. 4 (2022): 393–402.

[29] T. Shiina, A. Ando, Y. Suto, et al., “Genomic Anatomy of a Premier Major Histocompatibility Complex Paralogous Region on Chromosome 1q21-q22,” Genome Research 11, no. 5 (2001): 789–802.

[30] E. J. Collins, D. N. Garboczi, M. N. Karpusas, et al., “The Three-dimensional Structure of a Class I Major Histocompatibility Complex Molecule Missing the Alpha 3 Domain of the Heavy Chain,” Proceedings of the National Academy of Sciences of the United States of America 92, no. 4 (1995): 1218–1221.

[31] P. Parham, “Function and Polymorphism of human Leukocyte Antigen-A, B, C Molecules,” American Journal of Medicine 85, no. 6A (1988): 2–5.

[32] P. A. Reche and E. L. Reinherz, “Sequence Variability Analysis of human Class I and Class II MHC Molecules: Functional and Structural Correlates of Amino Acid Polymorphisms,” Journal of Molecular Biology 331, no. 3 (2003): 623–641.

[33] J. Kelley, L. Walter, and J. Trowsdale, “Comparative Genomics of Major Histocompatibility Complexes,” Immunogenetics 56, no. 10 (2005): 683–695.

[34] K. M. Ashby and K. A. Hogquist, “Author Correction: A Guide to Thymic Selection of T Cells,” Nature Reviews Immunology 23, no. 10 (2023): 697.

[35] K. A. Hogquist, S. C. Jameson, W. R. Heath, et al., “T Cell Receptor Antagonist Peptides Induce Positive Selection,” Cell 76, no. 1 (1994): 17–27.

[36] J. Zerrahn, W. Held, and D. H. Raulet, “The MHC Reactivity of the T Cell Repertoire Prior to Positive and Negative Selection,” Cell 88, no. 5 (1997): 627–636.

[37] J. D. Stone, A. S. Chervin, and D. M. Kranz, “T-cell Receptor Binding Affinities and Kinetics: Impact on T-cell Activity and Specificity,” Immunology 126, no. 2 (2009): 165–176.

[38] M. L. Dustin, “Recent Advances in Understanding TCR Signaling: A Synaptic Perspective,” Faculty Reviews 12 (2023): 25.

[39] K. Takada and S. C. Jameson, “Naive T Cell Homeostasis: From Awareness of Space to a Sense of Place,” Nature Reviews Immunology 9, no. 12 (2009): 823–832.

[40] H. G. Ljunggren and K. Kärre, “In Search of the ‘Missing Self’: MHC Molecules and NK Cell Recognition,” Immunology Today 11, no. 7 (1990): 237–244.

[41] J. Trowsdale, “Genetic and Functional Relationships Between MHC and NK Receptor Genes,” Immunity 15, no. 3 (2001): 363–374.

[42] M. J. W. Sim, B. Li, and E. O. Long, “Peptide-specific Natural Killer Cell Receptors,” Oxford Open Immunology 6, no. 1 (2025): iqaf003.

[43] M. Shiroishi, K. Tsumoto, K. Amano, et al., “Human Inhibitory Receptors Ig-Like Transcript 2 (ILT2) and ILT4 Compete With CD8 for MHC Class I Binding and Bind Preferentially to HLA-G,” Proceedings of the National Academy of Sciences of the United States of America 100, no. 15 (2003): 8856–8861.

[44] V. M. Braud, D. S. Allan, C. A. O'Callaghan, et al., “HLA-E Binds to Natural Killer Cell Receptors CD94/NKG2A, B and C,” Nature 391, no. 6669 (1998): 795–799.

[45] N. Lee, M. Llano, M. Carretero, et al., “HLA-E Is a Major Ligand for the Natural Killer Inhibitory Receptor CD94/NKG2A,” Proceedings of the National Academy of Sciences of the United States of America 95, no. 9 (1998): 5199–5204.

[46] F. Borrego, M. Ulbrecht, E. H. Weiss, et al., “Recognition of human Histocompatibility Leukocyte Antigen (HLA)-E Complexed With HLA Class I Signal Sequence-derived Peptides by CD94/NKG2 Confers Protection From Natural Killer Cell-mediated Lysis,” Journal of Experimental Medicine 187, no. 5 (1998): 813–818.

[47] B. K. Kaiser, J. C. Pizarro, J. Kerns, et al., “Structural Basis for NKG2A/CD94 Recognition of HLA-E,” Proceedings of the National Academy of Sciences of the United States of America 105, no. 18 (2008): 6696–6701.

[48] S. Bauer, V. Groh, J. Wu, et al., “Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-inducible MICA,” Science 285, no. 5428 (1999): 727–729.

[49] D. S. Katikaneni and L. Jin, “B Cell MHC Class II Signaling: A Story of Life and Death,” Human Immunology 80, no. 1 (2019): 37–43.

[50] K. L. Hilligan and F. Ronchese, “Antigen Presentation by Dendritic Cells and Their Instruction of CD4+ T Helper Cell Responses,” Cellular & Molecular Immunology 17, no. 6 (2020): 587–599.

[51] S. Yang, M. Zhao, and S. Jia, “Macrophage: Key Player in the Pathogenesis of Autoimmune Diseases,” Frontiers in Immunology 14 (2023): 1080310.

[52] M. Siljestam and C. Rueffler, “Heterozygote Advantage Can Explain the Extraordinary Diversity of Immune Genes,” Elife 13 (2024): e94587.

[53] V. Matzaraki, V. Kumar, C. Wijmenga, et al., “The MHC Locus and Genetic Susceptibility to Autoimmune and Infectious Diseases,” Genome Biology 18, no. 1 (2017): 76.

[54] J. Kaufman, “Unfinished Business: Evolution of the MHC and the Adaptive Immune System of Jawed Vertebrates,” Annual Review of Immunology 36 (2018): 383–409.

[55] P. A. Ott, Z. Hu, D. B. Keskin, et al., “An Immunogenic Personal Neoantigen Vaccine for Patients With Melanoma,” Nature 547, no. 7662 (2017): 217–221.

[56] A. R. Rappaport, C. Kyi, M. Lane, et al., “A Shared Neoantigen Vaccine Combined With Immune Checkpoint Blockade for Advanced Metastatic Solid Tumors: Phase 1 Trial Interim Results,” Nature Medicine 30, no. 4 (2024): 1013–1022.

[57] J. Li, Y. Ju, M. Jiang, et al., “Epitope-Based Vaccines: The Next Generation of Promising Vaccines against Bacterial Infection,” Vaccines (Basel) 13, no. 3 (2025): 248.

[58] G. A. Tannock, H. Kim, and L. Xue, “Why Are Vaccines Against Many human Viral Diseases Still Unavailable; an Historic Perspective?,” Journal of Medical Virology 92, no. 2 (2020): 129–138.

[59] K. Zhang, Y. Zhang, P. Xiang, et al., “Advances in T Cell-Based Cancer Immunotherapy: From Fundamental Mechanisms to Clinical Prospects,” Molecular Pharmaceutics 22, no. 6 (2025): 2807–2829.

[60] P. Shafer, L. M. Kelly, and V. Hoyos, “Cancer Therapy with TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects,” Frontiers in Immunology 13 (2022): 835762.

[61] S. J. Rodig, D. Gusenleitner, D. G. Jackson, et al., “MHC Proteins Confer Differential Sensitivity to CTLA-4 and PD-1 Blockade in Untreated Metastatic Melanoma,” Science Translational Medicine 10, no. 450 (2018): eaar3342.

[62] N. A. Rizvi, M. D. Hellmann, A. Snyder, et al., “Cancer Immunology. Mutational Landscape Determines Sensitivity to PD-1 Blockade in Non-small Cell Lung Cancer,” Science 348, no. 6230 (2015): 124–128.

[63] D. Karati, S. Meur, S. Das, et al., “Peptide-based Drugs in Immunotherapy: Current Advances and Future Prospects,” Medical Oncology 42, no. 5 (2025): 177.

[64] T. Nakamura, T. Shirouzu, K. Nakata, et al., “The Role of Major Histocompatibility Complex in Organ Transplantation- Donor Specific Anti-Major Histocompatibility Complex Antibodies Analysis Goes to the Next Stage,” International Journal of Molecular Sciences 20, no. 18 (2019): 4544.

[65] P. D. Katsikis, K. J. Ishii, and C. Schliehe, “Challenges in Developing Personalized Neoantigen Cancer Vaccines,” Nature Reviews Immunology 24, no. 3 (2024): 213–227.

[66] S. Jo, S. Das, A. Williams, et al., “Endowing Universal CAR T-cell With Immune-evasive Properties Using TALEN-gene Editing,” Nature Communications 13, no. 1 (2022): 3453.

[67] A. Fenis, O. Demaria, L. Gauthier, et al., “New Immune Cell Engagers for Cancer Immunotherapy,” Nature Reviews Immunology 24, no. 7 (2024): 471–486.

[68] A. Y. Chang, R. S. Gejman, E. J. Brea, et al., “Opportunities and Challenges for TCR Mimic Antibodies in Cancer Therapy,” Expert Opinion on Biological Therapy 16, no. 8 (2016): 979–987.

[69] Y. R. Li, Y. Zhu, T. Halladay, et al., “In Vivo CAR Engineering for Immunotherapy,” Nature Reviews Immunology 25, no. 10 (2025): 725–744.

[70] A. M. Cornel, I. L. Mimpen, and S. Nierkens, “MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy,” Cancers (Basel) 12, no. 7 (2020): 1760.

[71] L. R. Neal, S. R. Bailey, M. M. Wyatt, et al., “The Basics of Artificial Antigen Presenting Cells in T Cell-Based Cancer Immunotherapies,” Journal of Immunology Research and Therapy 2, no. 1 (2017): 68–79.

[72] J. D. Benitez Fuentes, J. Bartolome Arcilla, K. Mohamed Mohamed, et al., “Targeting of Non-Classical Human Leukocyte Antigens as Novel Therapeutic Strategies in Cancer,” Cancers (Basel) 16, no. 24 (2024): 4266.

[73] O. K. Dagher and A. D. Posey, “Forks in the Road for CAR T and CAR NK Cell Cancer Therapies,” Nature Immunology 24, no. 12 (2023): 1994–2007.

[74] D. E. Geraghty, M. Stockschleader, A. Ishitani, et al., “Polymorphism at the HLA-E Locus Predates Most HLA-A and -B Polymorphism,” Human Immunology 33, no. 3 (1992): 174–184.

[75] C. A. O'Callaghan, J. Tormo, B. E. Willcox, et al., “Structural Features Impose Tight Peptide Binding Specificity in the Nonclassical MHC Molecule HLA-E,” Molecular Cell 1, no. 4 (1998): 531–541.

[76] V. M. Braud, D. S. Allan, D. Wilson, et al., “TAP- and Tapasin-dependent HLA-E Surface Expression Correlates With the Binding of an MHC Class I Leader Peptide,” Current Biology 8, no. 1 (1998): 1–10.

[77] N. Lee, D. R. Goodlett, A. Ishitani, et al., “HLA-E Surface Expression Depends on Binding of TAP-dependent Peptides Derived From Certain HLA Class I Signal Sequences,” Journal of Immunology 160, no. 10 (1998): 4951–4960.

[78] N. van Montfoort, L. Borst, M. J. Korrer, et al., “NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines,” Cell 175, no. 7 (2018): 1744–1755 e15.

[79] D. E. Speiser, M. J. Pittet, D. Valmori, et al., “In Vivo Expression of Natural Killer Cell Inhibitory Receptors by human Melanoma-specific Cytolytic T Lymphocytes,” Journal of Experimental Medicine 190, no. 6 (1999): 775–782.

[80] Z. Lin, A. A. Bashirova, M. Viard, et al., “HLA Class I Signal Peptide Polymorphism Determines the Level of CD94/NKG2-HLA-E-mediated Regulation of Effector Cell Responses,” Nature Immunology 24, no. 7 (2023): 1087–1097.

[81] M. Vales-Gomez, H. T. Reyburn, R. A. Erskine, et al., “Kinetics and Peptide Dependency of the Binding of the Inhibitory NK Receptor CD94/NKG2-A and the Activating Receptor CD94/NKG2-C to HLA-E,” Embo Journal 18, no. 15 (1999): 4250–4260.

[82] L. L. Lanier, B. Corliss, J. Wu, et al., “Association of DAP12 With Activating CD94/NKG2C NK Cell Receptors,” Immunity 8, no. 6 (1998): 693–701.

[83] M. Abd Hamid, R. Z. Wang, and X. Yao, “Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8(+) Tumor-Infiltrating T Lymphocyte Responses,” Cancer Immunology Research 7, no. 8 (2019): 1293–1306.

[84] N. Lauterbach, L. Wieten, H. E. Popeijus, et al., “HLA-E Regulates NKG2C+ Natural Killer Cell Function Through Presentation of a Restricted Peptide Repertoire,” Human Immunology 76, no. 8 (2015): 578–586.

[85] B. I. Pereira, O. P. Devine, M. Vukmanovic-Stejic, et al., “Senescent Cells Evade Immune Clearance via HLA-E-mediated NK and CD8(+) T Cell Inhibition,” Nature Communications 10, no. 1 (2019): 2387.

[86] X. Wang, H. Xiong, and Z. Ning, “Implications of NKG2A in Immunity and Immune-mediated Diseases,” Frontiers in Immunology 13 (2022): 960852.

[87] H. R. Sharpe, G. Bowyer, S. Brackenridge, et al., “HLA-E: Exploiting Pathogen-host Interactions for Vaccine Development,” Clinical and Experimental Immunology 196, no. 2 (2019): 167–177.

[88] P. Romero, C. Ortega, A. Palma, et al., “Expression of CD94 and NKG2 Molecules on human CD4(+) T Cells in Response to CD3-mediated Stimulation,” Journal of Leukocyte Biology 70, no. 2 (2001): 219–224.

[89] X. X. Tang, H. Shimada, and N. Ikegaki, “Clinical Relevance of CD4 Cytotoxic T Cells in High-Risk Neuroblastoma,” Frontiers in Immunology 12 (2021): 650427.

[90] L. Voogd, C. Riou, T. J. Scriba, et al., “HLA-E/Mtb Specific CD4(+) and CD8(+) T Cells Have a Memory Phenotype in Individuals With TB Infection,” Frontiers in Immunology 15 (2024): 1505329.

[91] V. Cazzetta, E. Bruni, S. Terzoli, et al., “NKG2A expression Identifies a Subset of human Vdelta2 T Cells Exerting the Highest Antitumor Effector Functions,” Cell Reports 37, no. 3 (2021): 109871.

[92] H. Fausther-Bovendo, N. Wauquier, J. Cherfils-Vicini, et al., “NKG2C is a Major Triggering Receptor Involved in the V[delta]1 T Cell-mediated Cytotoxicity Against HIV-infected CD4 T Cells,” Aids 22, no. 2 (2008): 217–226.

[93] D. Krijgsman, J. Roelands, W. Hendrickx, et al., “HLA-G: A New Immune Checkpoint in Cancer?,” International Journal of Molecular Sciences 21, no. 12 (2020): 4528.

[94] L. A. Koopman, H. D. Kopcow, B. Rybalov, et al., “Human Decidual Natural Killer Cells Are a Unique NK Cell Subset With Immunomodulatory Potential,” Journal of Experimental Medicine 198, no. 8 (2003): 1201–1212.

[95] S. Rajagopalan and E. O. Long, “Cellular Senescence Induced by CD158d Reprograms Natural Killer Cells to Promote Vascular Remodeling,” Proceedings of the National Academy of Sciences of the United States of America 109, no. 50 (2012): 20596–20601.

[96] C. L. Wu, J. Caumartin, G. Amodio, et al., “Inhibition of iNKT Cells by the HLA-G-ILT2 Checkpoint and Poor Stimulation by HLA-G-Expressing Tolerogenic DC,” Frontiers in Immunology 11 (2020): 608614.

[97] G. T. Ho, A. A. Celik, T. Huyton, et al., “NKG2A/CD94 Is a New Immune Receptor for HLA-G and Distinguishes Amino Acid Differences in the HLA-G Heavy Chain,” International Journal of Molecular Sciences 21, no. 12 (2020): 4362.

[98] S. Kovats, E. K. Main, C. Librach, et al., “A Class I Antigen, HLA-G, Expressed in human Trophoblasts,” Science 248, no. 4952 (1990): 220–223.

[99] S. Liang, V. Ristich, H. Arase, et al., “Modulation of Dendritic Cell Differentiation by HLA-G and ILT4 Requires the IL-6–STAT3 Signaling Pathway,” Proceedings of the National Academy of Sciences of the United States of America 105, no. 24 (2008): 8357–8362.

[100] J. Baudhuin, J. Migraine, V. Faivre, et al., “Exocytosis Acts as a Modulator of the ILT4-mediated Inhibition of Neutrophil Functions,” Proceedings of the National Academy of Sciences of the United States of America 110, no. 44 (2013): 17957–17962.

[101] N. Kostlin, A. L. Ostermeir, B. Spring, et al., “HLA-G Promotes Myeloid-derived Suppressor Cell Accumulation and Suppressive Activity During human Pregnancy Through Engagement of the Receptor ILT4,” European Journal of Immunology 47, no. 2 (2017): 374–384.

[102] W. F. Garcia-Beltran, A. Holzemer, G. Martrus, et al., “Open Conformers of HLA-F Are High-affinity Ligands of the Activating NK-cell Receptor KIR3DS1,” Nature Immunology 17, no. 9 (2016): 1067–1074.

[103] J. P. Goodridge, A. Burian, N. Lee, et al., “HLA-F and MHC Class I Open Conformers Are Ligands for NK Cell Ig-Like Receptors,” Journal of Immunology 191, no. 7 (2013): 3553–3562.

[104] T. P. Cao, A. Shahine, L. R. Cox, et al., “A Structural Perspective of How T Cell Receptors Recognize the CD1 family of Lipid Antigen-presenting Molecules,” Journal of Biological Chemistry 300, no. 8 (2024): 107511.

[105] M. S. Vincent, X. Xiong, E. P. Grant, et al., “CD1a-, b-, and c-restricted TCRs Recognize both Self and Foreign Antigens,” Journal of Immunology 175, no. 10 (2005): 6344–6351.

[106] J. F. Reijneveld, T. A. Ocampo, A. Shahine, et al., “Human Gammadelta T Cells Recognize CD1b by Two Distinct Mechanisms,” Proceedings of the National Academy of Sciences of the United States of America 117, no. 37 (2020): 22944–22952.

[107] I. Van Rhijn and J. L. Nours, “CD1 and MR1 Recognition by human Gammadelta T Cells,” Molecular Immunology 133 (2021): 95–100.

[108] M. Wegrecki, T. A. Ocampo, S. D. Gunasinghe, et al., “Atypical Sideways Recognition of CD1a by Autoreactive Gammadelta T Cell Receptors,” Nature Communications 13, no. 1 (2022): 3872.

[109] M. Salou, R. A. Paiva, and O. Lantz, “Development and Functions of MAIT Cells,” Annual Review of Immunology 43, no. 1 (2025): 253–283.

[110] H. F. Koay, N. A. Gherardin, C. Xu, et al., “Diverse MR1-restricted T Cells in Mice and Humans,” Nature Communications 10, no. 1 (2019): 2243.

[111] J. Le Nours, N. A. Gherardin, S. H. Ramarathinam, et al., “A Class of Gammadelta T Cell Receptors Recognize the Underside of the Antigen-presenting Molecule MR1,” Science 366, no. 6472 (2019): 1522–1527.

[112] V. Braud, E. Y. Jones, and A. McMichael, “The human Major Histocompatibility Complex Class Ib Molecule HLA-E Binds Signal Sequence-derived Peptides With Primary Anchor Residues at Positions 2 and 9,” European Journal of Immunology 27, no. 5 (1997): 1164–1169.

[113] C. Thomas and R. Tampé, “MHC I Chaperone Complexes Shaping Immunity,” Current Opinion in Immunology 58 (2019): 9–15.

[114] W. He, E. Gea-Mallorqui, H. Colin-York, et al., “Intracellular Trafficking of HLA-E and Its Regulation,” Journal of Experimental Medicine 220, no. 8 (2023): e20221941.

[115] L. C. Walters, K. Harlos, S. Brackenridge, et al., “Pathogen-derived HLA-E Bound Epitopes Reveal Broad Primary Anchor Pocket Tolerability and Conformationally Malleable Peptide Binding,” Nature Communications 9, no. 1 (2018): 3137.

[116] R. K. Strong, M. A. Holmes, P. Li, et al., “HLA-E Allelic Variants. Correlating Differential Expression, Peptide Affinities, Crystal Structures, and Thermal Stabilities,” Journal of Biological Chemistry 278, no. 7 (2003): 5082–5090.

[117] L. C. Walters, D. Rozbesky, K. Harlos, et al., “Primary and Secondary Functions of HLA-E Are Determined by Stability and Conformation of the Peptide-bound Complexes,” Cell Reports 39, no. 11 (2022): 110959.

[118] M. L. Fahnestock, I. Tamir, L. Narhi, et al., “Thermal Stability Comparison of Purified Empty and Peptide-filled Forms of a Class I MHC Molecule,” Science 258, no. 5088 (1992): 1658–1662.

[119] C. S. Morgan, J. M. Holton, B. D. Olafson, et al., “Circular Dichroism Determination of Class I MHC-peptide Equilibrium Dissociation Constants,” Protein Science 6, no. 8 (1997): 1771–1773.

[120] W. He, A. Damianou, I. Vendrell, et al., “A Cytoplasmic Motif in HLA-E That Drives Clathrin-mediated Endocytosis and VCP-associated Postendocytic Trafficking,” Proceedings of the National Academy of Sciences of the United States of America 122, no. 43 (2025): e2514956122.

[121] P. Tomasec, V. M. Braud, C. Rickards, et al., “Surface Expression of HLA-E, an Inhibitor of Natural Killer Cells, Enhanced by human cytomegalovirus gpUL40,” Science 287, no. 5455 (2000): 1031.

[122] J. Nattermann, H. D. Nischalke, V. Hofmeister, et al., “HIV-1 Infection Leads to Increased HLA-E Expression Resulting in Impaired Function of Natural Killer Cells,” Antiviral Therapy 10, no. 1 (2005): 95–107.

[123] J. E. Grotzke, M. J. Harriff, A. C. Siler, et al., “The Mycobacterium Tuberculosis Phagosome Is a HLA-I Processing Competent Organelle,” Plos Pathogens 5, no. 4 (2009): e1000374.

[124] C. Powers, V. DeFilippis, D. Malouli, et al., “Cytomegalovirus Immune Evasion,” Current Topics in Microbiology and Immunology 325 (2008): 333–359.

[125] S. L. Gall, L. Erdtmann, S. Benichou, et al., “Nef Interacts With the Mu Subunit of Clathrin Adaptor Complexes and Reveals a Cryptic Sorting Signal in MHC I Molecules,” Immunity 8, no. 4 (1998): 483–495.

[126] M. Williams, J. F. Roeth, M. R. Kasper, et al., “Direct Binding of human Immunodeficiency Virus Type 1 Nef to the Major Histocompatibility Complex Class I (MHC-I) Cytoplasmic Tail Disrupts MHC-I Trafficking,” Journal of Virology 76, no. 23 (2002): 12173–12184.

[127] E. M. de Kruijf, A. Sajet, J. G. van Nes, et al., “HLA-E and HLA-G Expression in Classical HLA Class I-negative Tumors Is of Prognostic Value for Clinical Outcome of Early Breast Cancer Patients,” Journal of Immunology 185, no. 12 (2010): 7452–7459.

[128] B. Seliger, S. Jasinski-Bergner, D. Quandt, et al., “HLA-E Expression and Its Clinical Relevance in human Renal Cell Carcinoma,” Oncotarget 7, no. 41 (2016): 67360–67372.

[129] M. Allard, R. Oger, V. Vignard, et al., “Serum Soluble HLA-E in Melanoma: A New Potential Immune-related Marker in Cancer,” PLoS ONE 6, no. 6 (2011): e21118.

[130] F. Morandi, G. Cangemi, S. Barco, et al., “Plasma Levels of Soluble HLA-E and HLA-F at Diagnosis May Predict Overall Survival of Neuroblastoma Patients,” BioMed Research International 2013 (2013): 956878.

[131] B. Wagner, F. da Silva Nardi, S. Schramm, et al., “HLA-E Allelic Genotype Correlates With HLA-E Plasma Levels and Predicts Early Progression in Chronic Lymphocytic Leukemia,” Cancer 123, no. 5 (2017): 814–823.

[132] P. E. Jensen, B. A. Sullivan, L. M. Reed-Loisel, et al., “Qa-1, a Nonclassical Class I Histocompatibility Molecule With Roles in Innate and Adaptive Immunity,” Immunologic Research 29, no. 1–3 (2004): 81–92.

[133] J. R. Kraft, R. E. Vance, J. Pohl, et al., “Analysis of Qa-1(b) Peptide Binding Specificity and the Capacity of CD94/NKG2A to Discriminate Between Qa-1-peptide Complexes,” Journal of Experimental Medicine 192, no. 5 (2000): 613–624.

[134] T. van Hall, C. C. Oliveira, S. A. Joosten, et al., “The Other Janus Face of Qa-1 and HLA-E: Diverse Peptide Repertoires in Times of Stress,” Microbes and Infection 12, no. 12–13 (2010): 910–918.

[135] L. Zeng, L. C. Sullivan, J. P. Vivian, et al., “A Structural Basis for Antigen Presentation by the MHC Class Ib Molecule, Qa-1b,” Journal of Immunology 188, no. 1 (2012): 302–310.

[136] C. J. Aldrich, A. DeCloux, A. S. Woods, et al., “Identification of a Tap-dependent Leader Peptide Recognized by Alloreactive T Cells Specific for a Class Ib Antigen,” Cell 79, no. 4 (1994): 649–658.

[137] A. DeCloux, A. S. Woods, R. J. Cotter, et al., “Dominance of a Single Peptide Bound to the Class I(B) Molecule, Qa-1b,” Journal of Immunology 158, no. 5 (1997): 2183–2191.

[138] T. Kambayashi, J. R. Kraft-Leavy, J. G. Dauner, et al., “The Nonclassical MHC Class I Molecule Qa-1 Forms Unstable Peptide Complexes,” Journal of Immunology 172, no. 3 (2004): 1661–1669.

[139] M. Bouvier and D. C. Wiley, “Importance of Peptide Amino and Carboxyl Termini to the Stability of MHC Class I Molecules,” Science 265, no. 5170 (1994): 398–402.

[140] H. L. Wu, R. W. Wiseman, C. M. Hughes, et al., “The Role of MHC-E in T Cell Immunity Is Conserved Among Humans, Rhesus Macaques, and Cynomolgus Macaques,” Journal of Immunology 200, no. 1 (2018): 49–60.

[141] H. Brochu, R. Wang, T. Tollison, et al., “Alternative Splicing and Genetic Variation of mhc-e: Implications for rhesus cytomegalovirus-based Vaccines,” Communications Biology 5, no. 1 (2022): 1387.

[142] K. E. van Meijgaarden, M. C. Haks, N. Caccamo, et al., “Human CD8+ T-cells Recognizing Peptides From Mycobacterium Tuberculosis (Mtb) Presented by HLA-E Have an Unorthodox Th2-Like, Multifunctional, Mtb Inhibitory Phenotype and Represent a Novel human T-cell Subset,” Plos Pathogens 11, no. 3 (2015): e1004671.

[143] A. S. Heinzel, J. E. Grotzke, R. A. Lines, et al., “HLA-E-dependent Presentation of Mtb-derived Antigen to human CD8+ T Cells,” Journal of Experimental Medicine 196, no. 11 (2002): 1473–1481.

[144] N. Caccamo, G. Pietra, L. C. Sullivan, et al., “Human CD8 T Lymphocytes Recognize Mycobacterium Tuberculosis Antigens Presented by HLA-E During Active Tuberculosis and Express Type 2 Cytokines,” European Journal of Immunology 45, no. 4 (2015): 1069–1081.

[145] S. A. Joosten, K. E. van Meijgaarden, P. C. van Weeren, et al., “Mycobacterium Tuberculosis Peptides Presented by HLA-E Molecules Are Targets for human CD8 T-cells With Cytotoxic as Well as Regulatory Activity,” Plos Pathogens 6, no. 2 (2010): e1000782.

[146] C. McMurtrey, M. J. Harriff, G. M. Swarbrick, et al., “T Cell Recognition of Mycobacterium Tuberculosis Peptides Presented by HLA-E Derived From Infected human Cells,” PLoS ONE 12, no. 11 (2017): e0188288.

[147] R. Salerno-Goncalves, M. Fernandez-Vina, D. M. Lewinsohn, et al., “Identification of a human HLA-E-restricted CD8+ T Cell Subset in Volunteers Immunized With Salmonella Enterica Serovar Typhi Strain Ty21a Typhoid Vaccine,” Journal of Immunology 173, no. 9 (2004): 5852–5862.

[148] R. Salerno-Goncalves, R. Wahid, and M. B. Sztein, “Ex Vivo Kinetics of Early and Long-term Multifunctional human Leukocyte Antigen E-specific CD8+ Cells in Volunteers Immunized With the Ty21a Typhoid Vaccine,” Clinical and Vaccine Immunology: CVI 17, no. 9 (2010): 1305–1314.

[149] G. Pietra, C. Romagnani, P. Mazzarino, et al., “HLA-E-restricted Recognition of cytomegalovirus-derived Peptides by human CD8+ Cytolytic T Lymphocytes,” Proceedings of the National Academy of Sciences of the United States of America 100, no. 19 (2003): 10896–10901.

[150] D. Schulte, M. Vogel, B. Langhans, et al., “The HLA-E(R)/HLA-E(R) Genotype Affects the Natural Course of hepatitis C Virus (HCV) Infection and Is Associated With HLA-E-restricted Recognition of an HCV-derived Peptide by Interferon-gamma-secreting human CD8(+) T Cells,” Journal of Infectious Diseases 200, no. 9 (2009): 1397–1401.

[151] H. Yang, H. Sun, S. Brackenridge, et al., “HLA-E-restricted SARS-CoV-2-specific T Cells From Convalescent COVID-19 Patients Suppress Virus Replication Despite HLA Class Ia Down-regulation,” Science Immunology 8, no. 84 (2023): eabl8881.

[152] P. Mazzarino, G. Pietra, P. Vacca, et al., “Identification of Effector-memory CMV-specific T Lymphocytes That Kill CMV-infected Target Cells in an HLA-E-restricted Fashion,” European Journal of Immunology 35, no. 11 (2005): 3240–3247.

[153] Y. Bian, S. Shang, S. Siddiqui, et al., “MHC Ib Molecule Qa-1 Presents Mycobacterium Tuberculosis Peptide Antigens to CD8+ T Cells and Contributes to Protection Against Infection,” Plos Pathogens 13, no. 5 (2017): e1006384.

[154] H. G. Bouwer, K. F. Lindahl, J. R. Baldridge, et al., “An H2-T MHC Class Ib Molecule Presents Listeria monocytogenes-derived Antigen to Immune CD8+ Cytotoxic T Cells,” Journal of Immunology 152, no. 11 (1994): 5352–5360.

[155] W. F. Lo, H. Ong, E. S. Metcalf, et al., “T Cell Responses to Gram-negative Intracellular Bacterial Pathogens: A Role for CD8+ T Cells in Immunity to Salmonella Infection and the Involvement of MHC Class Ib Molecules,” Journal of Immunology 162, no. 9 (1999): 5398–5406.

[156] M. J. Hogan, N. Maheshwari, B. E. Begg, et al., “Cryptic MHC-E Epitope From Influenza Elicits a Potent Cytolytic T Cell Response,” Nature Immunology 24, no. 11 (2023): 1933–1946.

[157] S. G. Hansen, H. L. Wu, B. J. Burwitz, et al., “Broadly Targeted CD8+ T Cell Responses Restricted by Major Histocompatibility Complex E,” Science 351, no. 6274 (2016): 714–720.

[158] S. G. Hansen, D. E. Zak, G. Xu, et al., “Prevention of Tuberculosis in rhesus Macaques by a cytomegalovirus-based Vaccine,” Nature Medicine 24, no. 2 (2018): 130–143.

[159] S. G. Hansen, J. Womack, I. Scholz, et al., “Cytomegalovirus Vectors Expressing Plasmodium Knowlesi Antigens Induce Immune Responses That Delay Parasitemia Upon Sporozoite Challenge,” PLoS ONE 14, no. 1 (2019): e0210252.

[160] B. J. Burwitz, P. K. Hashiguchi, M. Mansouri, et al., “MHC-E-Restricted CD8 + T Cells Target Hepatitis B Virus-Infected Human Hepatocytes,” Journal of Immunology 204, no. 8 (2020): 2169–2176.

[161] H. Yang, M. Rei, S. Brackenridge, et al., “HLA-E-restricted, Gag-specific CD8,” Science Immunology 6, no. 57 (2021): eabg1703.

[162] J. K. Hwang, D. J. Marston, M. Tuyishime, et al., “HLA-E-VL9 Antibodies Enhance NK Cell and CD8+ T Cell Cytotoxicity Against HIV-infected CD4+ T Cells,” bioRxiv in Press (2025).

[163] A. Bansal, M. N. Gehre, K. Qin, et al., “HLA-E-restricted HIV-1-specific CD8+ T Cell Responses in Natural Infection,” Journal of Clinical Investigation 131, no. 16 (2021): e148979.

[164] Z. Hannoun, Z. Lin, S. Brackenridge, et al., “Identification of Novel HIV-1-derived HLA-E-binding Peptides,” Immunology Letters 202 (2018): 65–72.

[165] V. K. Vuttaradhi, C. M. Vermelle, J. Y. Choi, et al., “CD8+ Regulatory T Cells,” Annual Review of Immunology (2025).

[166] L. Lu, H. J. Kim, M. B. Werneck, et al., “Regulation of CD8+ Regulatory T Cells: Interruption of the NKG2A-Qa-1 Interaction Allows Robust Suppressive Activity and Resolution of Autoimmune Disease,” Proceedings of the National Academy of Sciences of the United States of America 105, no. 49 (2008): 19420–19425.

[167] H. J. Kim, H. Nakagawa, J. Y. Choi, et al., “A Narrow T Cell Receptor Repertoire Instructs Thymic Differentiation of MHC Class Ib-restricted CD8+ Regulatory T Cells,” Journal of Clinical Investigation 134, no. 1 (2024): e170512.

[168] H. J. Kim, B. Verbinnen, X. Tang, et al., “Inhibition of Follicular T-helper Cells by CD8(+) Regulatory T Cells Is Essential for Self Tolerance,” Nature 467, no. 7313 (2010): 328–332.

[169] D. Hu, K. Ikizawa, L. Lu, et al., “Analysis of Regulatory CD8 T Cells in Qa-1-deficient Mice,” Nature Immunology 5, no. 5 (2004): 516–523.

[170] J. Y. Choi, S. K. Eskandari, S. Cai, et al., “Regulatory CD8 T Cells That Recognize Qa-1 Expressed by CD4 T-helper Cells Inhibit Rejection of Heart Allografts,” Proceedings of the National Academy of Sciences of the United States of America 117, no. 11 (2020): 6042–6046.

[171] H. Jiang, S. M. Canfield, M. P. Gallagher, et al., “HLA-E-restricted Regulatory CD8(+) T Cells Are Involved in Development and Control of human Autoimmune Type 1 Diabetes,” Journal of Clinical Investigation 120, no. 10 (2010): 3641–3650.

[172] G. Camilli, A. Cassotta, S. Battella, et al., “Regulation and Trafficking of the HLA-E Molecules During Monocyte-macrophage Differentiation,” Journal of Leukocyte Biology 99, no. 1 (2016): 121–130.

[173] S. Singhaviranon, J. P. Dempsey, A. T. Hagymasi, et al., “Low-avidity T Cells Drive Endogenous Tumor Immunity in Mice and Humans,” Nature Immunology 26, no. 2 (2025): 240–251.

[174] A. J. McMichael and L. J. Picker, “Unusual Antigen Presentation Offers New Insight Into HIV Vaccine Design,” Current Opinion in Immunology 46 (2017): 75–81.

[175] M. C. Verweij, S. G. Hansen, R. Iyer, et al., “Modulation of MHC-E Transport by Viral Decoy Ligands Is Required for RhCMV/SIV Vaccine Efficacy,” Science 372, no. 6541 (2021): eabe9233.

[176] N. Mamidi, F. F. De Silva, A. B. Vacas, et al., “Multifaceted Hydrogel Scaffolds: Bridging the Gap Between Biomedical Needs and Environmental Sustainability,” Advanced Healthcare Materials 13, no. 27 (2024): e2401195.

[177] Y. Li, Z. Li, Y. Tang, et al., “Unlocking the Therapeutic Potential of the NKG2A-HLA-E Immune Checkpoint Pathway in T Cells and NK Cells for Cancer Immunotherapy,” Journal for ImmunoTherapy of Cancer 12, no. 10 (2024): e009934.

[178] N. Jiang, Y. Yu, D. Wu, et al., “HLA and Tumour Immunology: Immune Escape, Immunotherapy and Immune-related Adverse Events,” Journal of Cancer Research and Clinical Oncology 149, no. 2 (2023): 737–747.

[179] J. G. Fisher, A. D. P. Doyle, L. V. Graham, et al., “Disruption of the NKG2A:HLA-E Immune Checkpoint Axis to Enhance NK Cell Activation Against Cancer,” Vaccines (Basel) 10, no. 12 (2022): 1993.

[180] P. Andre, C. Denis, C. Soulas, et al., “Anti-NKG2A mAb Is a Checkpoint Inhibitor That Promotes Anti-tumor Immunity by Unleashing both T and NK Cells,” Cell 175, no. 7 (2018): 1731–1743 e13.

[181] L. Borst, S. H. van der Burg, and T. van Hall, “The NKG2A-HLA-E Axis as a Novel Checkpoint in the Tumor Microenvironment,” Clinical Cancer Research 26, no. 21 (2020): 5549–5556.

[182] H. W. Tsao, S. Anderson, K. J. Finn, et al., “Targeting the Aminopeptidase ERAP Enhances Antitumor Immunity by Disrupting the NKG2A-HLA-E Inhibitory Checkpoint,” Immunity 57, no. 12 (2024): 2863–2878 e12.

[183] L. Saveanu, O. Carroll, V. Lindo, et al., “Concerted Peptide Trimming by human ERAP1 and ERAP2 Aminopeptidase Complexes in the Endoplasmic Reticulum,” Nature Immunology 6, no. 7 (2005): 689–697.

[184] S. Lopez-Verges, J. M. Milush, B. S. Schwartz, et al., “Expansion of a Unique CD57(+)NKG2Chi Natural Killer Cell Subset During Acute human cytomegalovirus Infection,” Proceedings of the National Academy of Sciences of the United States of America 108, no. 36 (2011): 14725–14732.

[185] M. Guma, M. Budt, A. Saez, et al., “Expansion of CD94/NKG2C+ NK Cells in Response to human cytomegalovirus-infected Fibroblasts,” Blood 107, no. 9 (2006): 3624–3631.

[186] C. L. Dulberger, C. P. McMurtrey, A. Hölzemer, et al., “Human Leukocyte Antigen F Presents Peptides and Regulates Immunity Through Interactions With NK Cell Receptors,” Immunity 46, no. 6 (2017): 1018–1029.e7.

[187] C. K. Burrows, G. Kosova, C. Herman, et al., “Expression Quantitative Trait Locus Mapping Studies in Mid-secretory Phase Endometrial Cells Identifies HLA-F and TAP2 as Fecundability-Associated Genes,” PLos Genet 12, no. 7 (2016): e1005858.

[188] S. Song, C. J. Miranda, L. Braun, et al., “Major Histocompatibility Complex Class I Molecules Protect Motor Neurons From Astrocyte-induced Toxicity in amyotrophic Lateral sclerosis,” Nature Medicine 22, no. 4 (2016): 397–403.

[189] S. Lunemann, A. Schöbel, J. Kah, et al., “Interactions between KIR3DS1 and HLA-F Activate Natural Killer Cells to Control HCV Replication in Cell Culture,” Gastroenterology 155, no. 5 (2018): 1366–1371.e3.

[190] J. P. Goodridge, A. Burian, N. Lee, et al., “HLA-F Complex Without Peptide Binds to MHC Class I Protein in the Open Conformer Form,” Journal of Immunology 184, no. 11 (2010): 6199–6208.

[191] J. P. Goodridge, N. Lee, A. Burian, et al., “HLA-F and MHC-I Open Conformers Cooperate in a MHC-I Antigen Cross-presentation Pathway,” Journal of Immunology 191, no. 4 (2013): 1567–1577.

[192] N. Lee and D. E. Geraghty, “HLA-F Surface Expression on B Cell and Monocyte Cell Lines Is Partially Independent From Tapasin and Completely Independent From TAP,” Journal of Immunology 171, no. 10 (2003): 5264–5271.

[193] N. Lee, A. Ishitani, and D. E. Geraghty, “HLA-F Is a Surface Marker on Activated Lymphocytes,” European Journal of Immunology 40, no. 8 (2010): 2308–2318.

[194] R. Hackmon, L. Pinnaduwage, J. Zhang, et al., “Definitive Class I human Leukocyte Antigen Expression in Gestational Placentation: HLA-F, HLA-E, HLA-C, and HLA-G in Extravillous Trophoblast Invasion on Placentation, Pregnancy, and Parturition,” American Journal of Reproductive Immunology 77, no. 6 (2017): e12643.

[195] A. Lin and W. H. Yan, “The Emerging Roles of Human Leukocyte Antigen-F in Immune Modulation and Viral Infection,” Frontiers in Immunology 10 (2019): 964.

[196] S. D. Wainwright, P. A. Biro, and C. H. Holmes, “HLA-F Is a Predominantly Empty, Intracellular, TAP-associated MHC Class Ib Protein With a Restricted Expression Pattern,” Journal of Immunology 164, no. 1 (2000): 319–328.

[197] L. H. Boyle, A. K. Gillingham, S. Munro, et al., “Selective Export of HLA-F by Its Cytoplasmic Tail,” Journal of Immunology 176, no. 11 (2006): 6464–6472.

[198] D. E. Geraghty, X. H. Wei, H. T. Orr, et al., “Human Leukocyte Antigen F (HLA-F). An Expressed HLA Gene Composed of a Class I Coding Sequence Linked to a Novel Transcribed Repetitive Element,” Journal of Experimental Medicine 171, no. 1 (1990): 1–18.

[199] J. Moscoso, J. I. Serrano-Vela, and A. Arnaiz-Villena, “MHC-F Polymorphism and Evolution,” Tissue Antigens 69, no. Suppl 1 (2007): 136–139.

[200] L. Closa, F. Vidal, M. J. Herrero, et al., “High-throughput Genotyping of HLA-G, HLA-F, MICA, and MICB and Analysis of Frequency Distributions in Healthy Blood Donors From Catalonia,” HLA 97, no. 5 (2021): 420–427.

[201] F. H. Pan, X. X. Liu, and W. Tian, “Characterization of HLA-F Polymorphism in Four Distinct Populations in Mainland China,” International Journal of Immunogenetics 40, no. 5 (2013): 369–376.

[202] R. Daza-Vamenta, G. Glusman, L. Rowen, et al., “Genetic Divergence of the rhesus macaque Major Histocompatibility Complex,” Genome Research 14, no. 8 (2004): 1501–1515.

[203] Y. Xu, H. Han, F. Zhang, et al., “Lesion human Leukocyte Antigen-F Expression Is Associated With a Poor Prognosis in Patients With Hepatocellular Carcinoma,” Oncology letters 9, no. 1 (2015): 300–304.

[204] X. Zhang, A. Lin, J. G. Zhang, et al., “Alteration of HLA-F and HLA I Antigen Expression in the Tumor Is Associated With Survival in Patients With Esophageal Squamous Cell Carcinoma,” International Journal of Cancer 132, no. 1 (2013): 82–89.

[205] S. Ishigami, T. Arigami, T. Setoyama, et al., “Clinical-pathological Implication of human Leukocyte Antigen-F-positive Gastric Adenocarcinoma,” Journal of Surgical Research 184, no. 2 (2013): 802–806.

[206] S. Lunemann, A. Schobel, J. Kah, et al., “Interactions between KIR3DS1 and HLA-F Activate Natural Killer Cells to Control HCV Replication in Cell Culture,” Gastroenterology 155, no. 5 (2018): 1366–1371 e3.

[207] G. Kumar, O. S. Date, K. S. Kim, et al., “Infection of human Amniotic and Endothelial Cells by Japanese Encephalitis Virus: Increased Expression of HLA-F,” Virology 471–473 (2014): 29–37.

[208] J. M. Jung, W. Ching, M. E. Baumdick, et al., “KIR3DS1 directs NK Cell-mediated Protection Against human adenovirus Infections,” Science Immunology 6, no. 63 (2021): eabe2942.

[209] T. F. Koyro, E. Kraus, S. Lunemann, et al., “Upregulation of HLA-F Expression by BK Polyomavirus Infection Induces Immune Recognition by KIR3DS1-positive Natural Killer Cells,” Kidney International 99, no. 5 (2021): 1140–1148.

[210] X. Chen, N. Sun, R. Li, et al., “Targeting HLA-F Suppresses the Proliferation of Glioma Cells via a Reduction in Hexokinase 2-dependent Glycolysis,” International Journal of Biological Sciences 17, no. 5 (2021): 1263–1276.

[211] M. H. Ravindranath, N. M. Ravindranath, C. J. Amato-Menker, et al., “Diversity in the HLA-I Recognition of HLA-F Monoclonal Antibodies: HLA-F or HLA-Ib Monospecific, HLA-E or HLA-G Bispecific Antibodies With or Without HLA-Ia Reactivity,” Antibodies (Basel) 13, no. 1 (2024): 8.

[212] S. Wang, J. Wang, Y. Xia, et al., “Harnessing the Potential of HLA-G in Cancer Therapy: Advances, Challenges, and Prospects,” Journal of Translational Medicine 22, no. 1 (2024): 130.

[213] M. Le Discorde, P. Moreau, P. Sabatier, et al., “Expression of HLA-G in human Cornea, an Immune-privileged Tissue,” Human Immunology 64, no. 11 (2003): 1039–1044.

[214] V. Cirulli, J. Zalatan, M. McMaster, et al., “The Class I HLA Repertoire of Pancreatic Islets Comprises the Nonclassical Class Ib Antigen HLA-G,” Diabetes 55, no. 5 (2006): 1214–1222.

[215] C. Menier, M. Rabreau, J. C. Challier, et al., “Erythroblasts Secrete the Nonclassical HLA-G Molecule From Primitive to Definitive Hematopoiesis,” Blood 104, no. 10 (2004): 3153–3160.

[216] V. Mallet, A. Blaschitz, L. Crisa, et al., “HLA-G in the human thymus: A Subpopulation of Medullary Epithelial but Not CD83(+) Dendritic Cells Expresses HLA-G as a Membrane-bound and Soluble Protein,” International Immunology 11, no. 6 (1999): 889–898.

[217] S. R. Ye, H. Yang, K. Li, et al., “Human Leukocyte Antigen G Expression: As a Significant Prognostic Indicator for Patients With Colorectal Cancer,” Modern Pathology 20, no. 3 (2007): 375–383.

[218] J. Bukur, B. Malenica, C. Huber, et al., “Altered Expression of Nonclassical HLA Class Ib Antigens in human Renal Cell Carcinoma and Its Association With Impaired Immune Response,” Human Immunology 64, no. 11 (2003): 1081–1092.

[219] B. Davidson, M. B. Elstrand, M. T. McMaster, et al., “HLA-G Expression in Effusions Is a Possible Marker of Tumor Susceptibility to Chemotherapy in Ovarian Carcinoma,” Gynecologic Oncology 96, no. 1 (2005): 42–47.

[220] C. B. Zhu, C. X. Wang, X. Zhang, et al., “Serum sHLA-G Levels: A Useful Indicator in Distinguishing Colorectal Cancer From Benign Colorectal Diseases,” International Journal of Cancer 128, no. 3 (2011): 617–622.

[221] N. Lila, A. Carpentier, C. Amrein, et al., “Implication of HLA-G Molecule in Heart-graft Acceptance,” Lancet 355, no. 9221 (2000): 2138.

[222] M. Lafon, C. Prehaud, F. Megret, et al., “Modulation of HLA-G Expression in human Neural Cells After Neurotropic Viral Infections,” Journal of Virology 79, no. 24 (2005): 15226–15237.

[223] J. V. D. Attia, C. E. Dessens, R. van de Water, et al., “The Molecular and Functional Characteristics of HLA-G and the Interaction With Its Receptors: Where to Intervene for Cancer Immunotherapy?,” International Journal of Molecular Sciences 21, no. 22 (2020): 8678.

[224] M. Colonna, F. Navarro, T. Bellon, et al., “A Common Inhibitory Receptor for Major Histocompatibility Complex Class I Molecules on human Lymphoid and Myelomonocytic Cells,” Journal of Experimental Medicine 186, no. 11 (1997): 1809–1818.

[225] M. Colonna, J. Samaridis, M. Cella, et al., “Human Myelomonocytic Cells Express an Inhibitory Receptor for Classical and Nonclassical MHC Class I Molecules,” Journal of Immunology 160, no. 7 (1998): 3096–3100.

[226] S. Rajagopalan and E. O. Long, “A human Histocompatibility Leukocyte Antigen (HLA)-G-specific Receptor Expressed on all Natural Killer Cells,” Journal of Experimental Medicine 189, no. 7 (1999): 1093–1100.

[227] B. K. Kaiser, F. Barahmand-Pour, W. Paulsene, et al., “Interactions Between NKG2x Immunoreceptors and HLA-E Ligands Display Overlapping Affinities and Thermodynamics,” Journal of Immunology 174, no. 5 (2005): 2878–2884.

[228] S. Djurisic and T. V. Hviid, “HLA Class Ib Molecules and Immune Cells in Pregnancy and Preeclampsia,” Frontiers in Immunology 5 (2014): 652.

[229] S. Rajagopalan, Y. T. Bryceson, S. P. Kuppusamy, et al., “Activation of NK Cells by an Endocytosed Receptor for Soluble HLA-G,” Plos Biology 4, no. 1 (2006): e9.

[230] E. Schwich, G. T. Hò, J. LeMaoult, et al., “Soluble HLA-G and HLA-G Bearing Extracellular Vesicles Affect ILT-2 Positive and ILT-2 Negative CD8 T Cells Complementary,” Frontiers in Immunology 11 (2020): 2046.

[231] P. J. Morales, J. L. Pace, J. S. Platt, et al., “Placental Cell Expression of HLA-G2 Isoforms Is Limited to the Invasive Trophoblast Phenotype,” Journal of Immunology 171, no. 11 (2003): 6215–6224.

[232] K. Y. HoWangYin, M. Loustau, J. Wu, et al., “Multimeric Structures of HLA-G Isoforms Function Through Differential Binding to LILRB Receptors,” Cellular and Molecular Life Sciences 69, no. 23 (2012): 4041–4049.

[233] M. Shiroishi, K. Kuroki, T. Ose, et al., “Efficient Leukocyte Ig-Like Receptor Signaling and Crystal Structure of Disulfide-linked HLA-G Dimer,” Journal of Biological Chemistry 281, no. 15 (2006): 10439–10447.

[234] A. Ishitani, N. Sageshima, N. Lee, et al., “Protein Expression and Peptide Binding Suggest Unique and Interacting Functional Roles for HLA-E, F, and G in Maternal-placental Immune Recognition,” Journal of Immunology 171, no. 3 (2003): 1376–1384.

[235] C. S. Clements, L. Kjer-Nielsen, J. McCluskey, et al., “Structural Studies on HLA-G: Implications for Ligand and Receptor Binding,” Human Immunology 68, no. 4 (2007): 220–226.

[236] B. Park, S. Lee, E. Kim, et al., “The Truncated Cytoplasmic Tail of HLA-G Serves a Quality-control Function in Post-ER Compartments,” Immunity 15, no. 2 (2001): 213–224.

[237] T. Arns, D. A. Antunes, J. R. Abella, et al., “Structural Modeling and Molecular Dynamics of the Immune Checkpoint Molecule HLA-G,” Frontiers in Immunology 11 (2020): 575076.

[238] S. K. Kshirsagar, S. M. Alam, S. Jasti, et al., “Immunomodulatory Molecules Are Released From the First Trimester and Term Placenta via Exosomes,” Placenta 33, no. 12 (2012): 982–990.

[239] R. Vento-Tormo, M. Efremova, R. A. Botting, et al., “Single-cell Reconstruction of the Early Maternal-fetal Interface in Humans,” Nature 563, no. 7731 (2018): 347–353.

[240] N. Rouas-Freiss, P. Moreau, J. LeMaoult, et al., “Role of the HLA-G Immune Checkpoint Molecule in Pregnancy,” Human Immunology 82, no. 5 (2021): 353–361.

[241] N. T. Al-Bayatee and A. H. Ad'hiah, “Soluble HLA-G Is Upregulated in Serum of Patients With Severe COVID-19,” Human Immunology 82, no. 10 (2021): 726–732.

[242] I. I. Slukvin, D. I. Watkins, and T. G. Golos, “Tissue Distribution of the mRNA for a rhesus Monkey Major Histocompatibility Class Ib Molecule, Mamu-AG,” Tissue Antigens 53, no. 3 (1999): 282–291.

[243] D. K. Langat, P. J. Morales, A. T. Fazleabas, et al., “Baboon Placentas Express Soluble and Membrane-bound Paan-AG Proteins Encoded by Alternatively Spliced Transcripts of the Class Ib Major Histocompatibility Complex Gene, Paan-AG,” Immunogenetics 54, no. 3 (2002): 164–173.

[244] Z. Cai, L. Wang, Y. Han, et al., “Immunoglobulin‑Like Transcript 4 and human Leukocyte Antigen‑G Interaction Promotes the Progression of human Colorectal Cancer,” International Journal of Oncology 54, no. 6 (2019): 1943–1954.

[245] R. Wan, Z. W. Wang, H. Li, et al., “Human Leukocyte Antigen-G Inhibits the Anti-Tumor Effect of Natural Killer Cells via Immunoglobulin-Like Transcript 2 in Gastric Cancer,” Cellular Physiology and Biochemistry 44, no. 5 (2017): 1828–1841.

[246] Y. Zhang, J. Zhao, L. Qiu, et al., “Co-expression of ILT4/HLA-G in human Non-small Cell Lung Cancer Correlates With Poor Prognosis and ILT4-HLA-G Interaction Activates ERK Signaling,” Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine 37, no. 8 (2016): 11187–11198.

[247] J. M. Lozano, R. Gonzalez, J. M. Kindelan, et al., “Monocytes and T Lymphocytes in HIV-1-positive Patients Express HLA-G Molecule,” Aids 16, no. 3 (2002): 347–351.

[248] G. Vlad, F. Piazza, A. Colovai, et al., “Interleukin-10 Induces the Upregulation of the Inhibitory Receptor ILT4 in Monocytes From HIV Positive Individuals,” Human Immunology 64, no. 5 (2003): 483–489.

[249] W. H. Yan, A. Lin, B. G. Chen, et al., “Induction of both Membrane-bound and Soluble HLA-G Expression in Active human cytomegalovirus Infection,” Journal of Infectious Diseases 200, no. 5 (2009): 820–826.

[250] P. J. Weng, Y. M. Fu, S. X. Ding, et al., “Elevation of Plasma Soluble human Leukocyte Antigen-G in Patients With Chronic hepatitis C Virus Infection,” Human Immunology 72, no. 5 (2011): 406–411.

[251] Q. Han, N. Li, Q. Zhu, et al., “Association of Serum Soluble human Leukocyte Antigen-G Levels With Chronic hepatitis B Virus Infection,” Clinical and Experimental Medicine 14, no. 1 (2014): 35–43.

[252] Y. Park, Y. Park, H. S. Lim, et al., “Soluble human Leukocyte Antigen-G Expression in hepatitis B Virus Infection and Hepatocellular Carcinoma,” Tissue Antigens 79, no. 2 (2012): 97–103.

[253] H. H. Xu, W. H. Yan, and A. Lin, “The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis,” Frontiers in Immunology 11 (2020): 1349.

[254] J. M. Martín-Villa, C. Vaquero-Yuste, M. Molina-Alejandre, et al., “HLA-G: Too Much or Too Little? Role in Cancer and Autoimmune Disease,” Frontiers in Immunology 13 (2022): 796054.

[255] A. D. Lázaro-Sánchez, P. Salces-Ortiz, L. I. Velásquez, et al., “HLA-G as a New Tumor Biomarker: Detection of Soluble Isoforms of HLA-G in the Serum and Saliva of Patients With Colorectal Cancer,” Clinical & Translational Oncology 22, no. 7 (2020): 1166–1171.

[256] C. Kirana, A. Ruszkiewicz, R. S. Stubbs, et al., “Soluble HLA-G Is a Differential Prognostic Marker in Sequential Colorectal Cancer Disease Stages,” International Journal of Cancer 140, no. 11 (2017): 2577–2586.

[257] P. Li, N. Wang, Y. Zhang, et al., “HLA-G/sHLA-G and HLA-G-Bearing Extracellular Vesicles in Cancers: Potential Role as Biomarkers,” Frontiers in Immunology 12 (2021): 791535.

[258] M. Zaborek-Lyczba, J. Lyczba, P. Mertowska, et al., “The HLA-G Immune Checkpoint Plays a Pivotal Role in the Regulation of Immune Response in Autoimmune Diseases,” International Journal of Molecular Sciences 22, no. 24 (2021): 13348.

[259] Y. Zhang, X. Jin, and J. Wang, “miR‑148a Modulates the Viability, Migration and Invasion of Oral Squamous Cell Carcinoma Cells by Regulating HLA‑G Expression,” Molecular Medicine Reports 20, no. 1 (2019): 795–801.

[260] X. C. Zeng, T. Zhang, D. H. Huang, et al., “RNA Interfering Targeting human Leukocyte Antigen-G Enhanced Immune Surveillance Mediated by the Natural Killer Cells on Hepatocellular Carcinoma,” Annals of Clinical and Laboratory Science 43, no. 2 (2013): 135–144.

[261] T. Wengenmayer, T. G. Poehlmann, and U. R. Markert, “Inhibition of HLA-G Production in JEG-3 Choriocarcinoma Cells by RNA Interference,” American Journal of Reproductive Immunology 51, no. 3 (2004): 189–191.

[262] D. M. Zajonc, “The CD1 family: Serving Lipid Antigens to T Cells Since the Mesozoic Era,” Immunogenetics 68, no. 8 (2016): 561–576.

[263] L. Evans and P. Barral, “CD1 molecules: Beyond Antigen Presentation,” Molecular Immunology 170 (2024): 1–8.

[264] M. Han, L. I. Hannick, M. DiBrino, et al., “Polymorphism of human CD1 Genes,” Tissue Antigens 54, no. 2 (1999): 122–127.

[265] M. Brigl and M. B. Brenner, “CD1: Antigen Presentation and T Cell Function,” Annual Review of Immunology 22 (2004): 817–890.

[266] A. Bendelac, “Positive Selection of Mouse NK1+ T Cells by CD1-expressing Cortical Thymocytes,” Journal of Experimental Medicine 182, no. 6 (1995): 2091–2096.

[267] F. Calabi, J. M. Jarvis, L. Martin, et al., “Two Classes of CD1 Genes,” European Journal of Immunology 19, no. 2 (1989): 285–292.

[268] C. Angenieux, J. Salamero, D. Fricker, et al., “Characterization of CD1e, a Third Type of CD1 Molecule Expressed in Dendritic Cells,” Journal of Biological Chemistry 275, no. 48 (2000): 37757–37764.

[269] C. Angénieux, V. Fraisier, B. Maître, et al., “The Cellular Pathway of CD1e in Immature and Maturing Dendritic Cells,” Traffic (Copenhagen, Denmark) 6, no. 4 (2005): 286–302.

[270] L. Teyton, “Role of Lipid Transfer Proteins in Loading CD1 Antigen-presenting Molecules,” Journal of Lipid Research 59, no. 8 (2018): 1367–1373.

[271] J. E. Gumperz, “The Ins and Outs of CD1 Molecules: Bringing Lipids Under Immunological Surveillance,” Traffic (Copenhagen, Denmark) 7, no. 1 (2006): 2–13.

[272] L. Van Kaer, L. Wu, and S. Joyce, “Mechanisms and Consequences of Antigen Presentation by CD1,” Trends in Immunology 37, no. 11 (2016): 738–754.

[273] M. Sugita, E. P. Grant, E. van Donselaar, et al., “Separate Pathways for Antigen Presentation by CD1 Molecules,” Immunity 11, no. 6 (1999): 743–752.

[274] M. Sugita, X. Cao, G. F. Watts, et al., “Failure of Trafficking and Antigen Presentation by CD1 in AP-3-deficient Cells,” Immunity 16, no. 5 (2002): 697–706.

[275] D. B. Moody and R. N. Cotton, “Four Pathways of CD1 Antigen Presentation to T Cells,” Current Opinion in Immunology 46 (2017): 127–133.

[276] G. De Libero and L. Mori, “Novel Insights Into Lipid Antigen Presentation,” Trends in Immunology 33, no. 3 (2012): 103–111.

[277] H. de la Salle, S. Mariotti, C. Angenieux, et al., “Assistance of Microbial Glycolipid Antigen Processing by CD1e,” Science 310, no. 5752 (2005): 1321–1324.

[278] F. Facciotti, M. Cavallari, C. Angenieux, et al., “Fine Tuning by human CD1e of Lipid-specific Immune Responses,” Proceedings of the National Academy of Sciences of the United States of America 108, no. 34 (2011): 14228–14233.

[279] D. Ly and D. B. Moody, “The CD1 Size Problem: Lipid Antigens, Ligands, and Scaffolds,” Cellular and Molecular Life Sciences 71, no. 16 (2014): 3069–3079.

[280] L. Mori and G. De Libero, “T Cells Specific for Lipid Antigens,” Immunologic Research 53, no. 1–3 (2012): 191–199.

[281] V. Briken, R. M. Jackman, S. Dasgupta, et al., “Intracellular Trafficking Pathway of Newly Synthesized CD1b Molecules,” Embo Journal 21, no. 4 (2002): 825–834.

[282] L. Scharf, N. S. Li, A. J. Hawk, et al., “The 2.5 Å Structure of CD1c in Complex With a Mycobacterial Lipid Reveals an Open Groove Ideally Suited for Diverse Antigen Presentation,” Immunity 33, no. 6 (2010): 853–862.

[283] M. Koch, V. S. Stronge, D. Shepherd, et al., “The Crystal Structure of human CD1d With and Without Alpha-galactosylceramide,” Nature Immunology 6, no. 8 (2005): 819–826.

[284] D. M. Zajonc, M. A. Elsliger, L. Teyton, et al., “Crystal Structure of CD1a in Complex With a Sulfatide Self Antigen at a Resolution of 2.15 A,” Nature Immunology 4, no. 8 (2003): 808–815.

[285] L. F. Garcia-Alles, G. Giacometti, C. Versluis, et al., “Crystal Structure of human CD1e Reveals a Groove Suited for Lipid-exchange Processes,” Proceedings of the National Academy of Sciences of the United States of America 108, no. 32 (2011): 13230–13235.

[286] M. Relloso, T. Y. Cheng, J. S. Im, et al., “pH-dependent Interdomain Tethers of CD1b Regulate Its Antigen Capture,” Immunity 28, no. 6 (2008): 774–786.

[287] B. Cuevas-Zuviria, M. Minguez-Toral, A. Diaz-Perales, et al., “Dynamic Plasticity of the Lipid Antigen-binding Site of CD1d Is Crucially Favoured by Acidic pH and Helper Proteins,” Scientific Reports 10, no. 1 (2020): 5714.

[288] N. Bushmarina, S. Tourne, G. Giacometti, et al., “Increased Flexibility and Liposome-binding Capacity of CD1e at Endosomal pH,” Febs Journal 278, no. 12 (2011): 2022–2033.

[289] F. Winau, V. Schwierzeck, R. Hurwitz, et al., “Saposin C Is Required for Lipid Presentation by human CD1b,” Nature Immunology 5, no. 2 (2004): 169–174.

[290] D. Zhou, C. Cantu, Y. Sagiv, et al., “Editing of CD1d-bound Lipid Antigens by Endosomal Lipid Transfer Proteins,” Science 303, no. 5657 (2004): 523–527.

[291] A. Kasmar, I. Van Rhijn, and D. B. Moody, “The Evolved Functions of CD1 During Infection,” Current Opinion in Immunology 21, no. 4 (2009): 397–403.

[292] D. Morita, K. Katoh, T. Harada, et al., “Trans-species Activation of human T Cells by rhesus Macaque CD1b Molecules,” Biochemical and Biophysical Research Communications 377, no. 3 (2008): 889–893.

[293] D. Morita, Y. Hattori, T. Nakamura, et al., “Major T Cell Response to a Mycolyl Glycolipid Is Mediated by CD1c Molecules in rhesus Macaques,” Infection and Immunity 81, no. 1 (2013): 311–316.

[294] M. Nakamatsu, N. Yamamoto, M. Hatta, et al., “Role of Interferon-gamma in Valpha14+ Natural Killer T Cell-mediated Host Defense Against Streptococcus pneumoniae Infection in Murine Lungs,” Microbes and Infection 9, no. 3 (2007): 364–374.

[295] K. Kawakami, N. Yamamoto, Y. Kinjo, et al., “Critical Role of Valpha14+ Natural Killer T Cells in the Innate Phase of Host Protection Against Streptococcus pneumoniae Infection,” European Journal of Immunology 33, no. 12 (2003): 3322–3330.

[296] W. Y. Lee, T. J. Moriarty, C. H. Wong, et al., “An Intravascular Immune Response to Borrelia burgdorferi Involves Kupffer Cells and iNKT Cells,” Nature Immunology 11, no. 4 (2010): 295–302.

[297] E. Tupin, M. R. Benhnia, Y. Kinjo, et al., “NKT Cells Prevent Chronic Joint Inflammation After Infection With Borrelia burgdorferi,” Proceedings of the National Academy of Sciences of the United States of America 105, no. 50 (2008): 19863–19868.

[298] M. Brigl, L. Bry, S. C. Kent, et al., “Mechanism of CD1d-restricted Natural Killer T Cell Activation During Microbial Infection,” Nature Immunology 4, no. 12 (2003): 1230–1237.

[299] J. Mattner, K. L. Debord, N. Ismail, et al., “Exogenous and Endogenous Glycolipid Antigens Activate NKT Cells During Microbial Infections,” Nature 434, no. 7032 (2005): 525–529.

[300] B. K. Chung, K. Tsai, L. L. Allan, et al., “Innate Immune Control of EBV-infected B Cells by Invariant Natural Killer T Cells,” Blood 122, no. 15 (2013): 2600–2608.

[301] C. De Santo, M. Salio, S. H. Masri, et al., “Invariant NKT Cells Reduce the Immunosuppressive Activity of Influenza A Virus-induced Myeloid-derived Suppressor Cells in Mice and Humans,” Journal of Clinical Investigation 118, no. 12 (2008): 4036–4048.

[302] B. Grubor-Bauk, A. Simmons, G. Mayrhofer, et al., “Impaired Clearance of herpes Simplex Virus Type 1 From Mice Lacking CD1d or NKT Cells Expressing the Semivariant V Alpha 14-J Alpha 281 TCR,” Journal of Immunology 170, no. 3 (2003): 1430–1434.

[303] H. E. Broxmeyer, A. Dent, S. Cooper, et al., “A Role for Natural Killer T Cells and CD1d Molecules in Counteracting Suppression of Hematopoiesis in Mice Induced by Infection With Murine cytomegalovirus,” Experimental Hematology 35, no. 4 Suppl 1 (2007): 87–93.

[304] K. Kakimi, L. G. Guidotti, Y. Koezuka, et al., “Natural Killer T Cell Activation Inhibits hepatitis B Virus Replication in Vivo,” Journal of Experimental Medicine 192, no. 7 (2000): 921–930.

[305] T. R. Johnson, S. Hong, L. Van Kaer, et al., “NK T Cells Contribute to Expansion of CD8(+) T Cells and Amplification of Antiviral Immune Responses to respiratory Syncytial Virus,” Journal of Virology 76, no. 9 (2002): 4294–4303.

[306] N. Rout, J. Greene, S. Yue, et al., “Loss of Effector and Anti-inflammatory Natural Killer T Lymphocyte Function in Pathogenic simian Immunodeficiency Virus Infection,” Plos Pathogens 8, no. 9 (2012): e1002928.

[307] D. C. Baiu, A. Sharma, J. L. Schehr, et al., “Human CD4(+) iNKT Cell Adoptive Immunotherapy Induces Anti-tumour Responses Against CD1d-negative EBV-driven B Lymphoma,” Immunology 172, no. 4 (2024): 627–640.

[308] M. V. Dhodapkar, M. D. Geller, D. H. Chang, et al., “A Reversible Defect in Natural Killer T Cell Function Characterizes the Progression of Premalignant to Malignant Multiple Myeloma,” Journal of Experimental Medicine 197, no. 12 (2003): 1667–1676.

[309] L. Song, S. Asgharzadeh, J. Salo, et al., “Valpha24-invariant NKT Cells Mediate Antitumor Activity via Killing of Tumor-associated Macrophages,” Journal of Clinical Investigation 119, no. 6 (2009): 1524–1536.

[310] K. Felio, H. Nguyen, C. C. Dascher, et al., “CD1-restricted Adaptive Immune Responses to Mycobacteria in human Group 1 CD1 Transgenic Mice,” Journal of Experimental Medicine 206, no. 11 (2009): 2497–2509.

[311] P. A. Sieling, D. Jullien, M. Dahlem, et al., “CD1 expression by Dendritic Cells in human Leprosy Lesions: Correlation With Effective Host Immunity,” Journal of Immunology 162, no. 3 (1999): 1851–1858.

[312] C. C. Dascher, K. Hiromatsu, X. Xiong, et al., “Immunization With a Mycobacterial Lipid Vaccine Improves Pulmonary Pathology in the guinea Pig Model of Tuberculosis,” International Immunology 15, no. 8 (2003): 915–925.

[313] T. Kawashima, Y. Norose, Y. Watanabe, et al., “Cutting Edge: Major CD8 T Cell Response to Live bacillus Calmette-Guerin Is Mediated by CD1 Molecules,” Journal of Immunology 170, no. 11 (2003): 5345–5348.

[314] L. Visvabharathy, S. Genardi, L. Cao, et al., “Group 1 CD1-restricted T Cells Contribute to Control of Systemic Staphylococcus aureus Infection,” Plos Pathogens 16, no. 4 (2020): e1008443.

[315] M. Lepore, C. de Lalla, S. R. Gundimeda, et al., “A Novel Self-lipid Antigen Targets human T Cells Against CD1c(+) Leukemias,” Journal of Experimental Medicine 211, no. 7 (2014): 1363–1377.

[316] C. Roura-Mir, L. Wang, T. Y. Cheng, et al., “Mycobacterium Tuberculosis Regulates CD1 Antigen Presentation Pathways Through TLR-2,” Journal of Immunology 175, no. 3 (2005): 1758–1766.

[317] K. Yakimchuk, C. Roura-Mir, K. G. Magalhaes, et al., “Borrelia Burgdorferi Infection Regulates CD1 Expression in human Cells and Tissues via IL1-beta,” European Journal of Immunology 41, no. 3 (2011): 694–705.

[318] D. Horst, R. J. Geerdink, A. M. Gram, et al., “Hiding Lipid Presentation: Viral Interference With CD1d-restricted Invariant Natural Killer T (iNKT) Cell Activation,” Viruses 4, no. 10 (2012): 2379–2399.

[319] G. Schonrich and M. J. Raftery, “CD1-Restricted T Cells during Persistent Virus Infections: ‘’Sympathy for the Devil,” Frontiers in Immunology 9 (2018): 545.

[320] A. Motsinger, D. W. Haas, A. K. Stanic, et al., “CD1d-restricted human Natural Killer T Cells Are Highly Susceptible to human Immunodeficiency Virus 1 Infection,” Journal of Experimental Medicine 195, no. 7 (2002): 869–879.

[321] X. Jiang, M. Zhang, Q. Lai, et al., “Restored Circulating Invariant NKT Cells Are Associated With Viral Control in Patients With Chronic hepatitis B,” PLoS ONE 6, no. 12 (2011): e28871.

[322] M. V. Dhodapkar, “Role of Natural Killer T (NKT) Cells in Myeloma Biology and Therapy,” Critical Reviews in Oncogenesis 29, no. 1 (2024): 63–68.

[323] Y. R. Li, Z. Li, Y. Zhu, et al., “Overcoming Ovarian Cancer Resistance and Evasion to CAR-T Cell Therapy by Harnessing Allogeneic CAR-NKT Cells,” Med 6, no. 10 (2025): 100804.

[324] J. L. Matsuda, T. Mallevaey, J. Scott-Browne, et al., “CD1d-restricted iNKT Cells, the ‘Swiss-Army Knife’ of the Immune System,” Current Opinion in Immunology 20, no. 3 (2008): 358–368.

[325] H. J. Ko, J. M. Lee, Y. J. Kim, et al., “Immunosuppressive Myeloid-derived Suppressor Cells Can be Converted Into Immunogenic APCs With the Help of Activated NKT Cells: An Alternative Cell-based Antitumor Vaccine,” Journal of Immunology 182, no. 4 (2009): 1818–1828.

[326] A. Torina, G. Guggino, M. P. La Manna, et al., “The Janus Face of NKT Cell Function in Autoimmunity and Infectious Diseases,” International Journal of Molecular Sciences 19, no. 2 (2018): 440.

[327] D. Poddighe, T. Maulenkul, G. Zhubanova, et al., “Natural Killer T (NKT) Cells in Autoimmune Hepatitis: Current Evidence From Basic and Clinical Research,” Cells 12, no. 24 (2023): 2854.

[328] L. Van Kaer and L. Wu, “Therapeutic Potential of Invariant Natural Killer T Cells in Autoimmunity,” Frontiers in Immunology 9 (2018): 519.

[329] R. E. Hunger, P. A. Sieling, M. T. Ochoa, et al., “Langerhans Cells Utilize CD1a and Langerin to Efficiently Present Nonpeptide Antigens to T Cells,” Journal of Clinical Investigation 113, no. 5 (2004): 701–708.

[330] D. B. Moody, D. C. Young, T. Y. Cheng, et al., “T Cell Activation by Lipopeptide Antigens,” Science 303, no. 5657 (2004): 527–531.

[331] J. H. Ye, Y. L. Chen, and G. Ogg, “CD1a and Skin T Cells: A Pathway for Therapeutic Intervention,” Clinical and Experimental Dermatology 49, no. 5 (2024): 450–458.

[332] J. H. Kim, Y. Hu, T. Yongqing, et al., “CD1a on Langerhans Cells Controls Inflammatory Skin Disease,” Nature Immunology 17, no. 10 (2016): 1159–1166.

[333] G. C. Monnot, M. Wegrecki, T. Y. Cheng, et al., “Staphylococcal Phosphatidylglycerol Antigens Activate human T Cells via CD1a,” Nature Immunology 24, no. 1 (2023): 110–122.

[334] A. de Jong and G. Ogg, “CD1a function in human Skin Disease,” Molecular Immunology 130 (2021): 14–19.

[335] M. Nieda, M. Okai, A. Tazbirkova, et al., “Therapeutic Activation of Valpha24+Vbeta11+ NKT Cells in human Subjects Results in Highly Coordinated Secondary Activation of Acquired and Innate Immunity,” Blood 103, no. 2 (2004): 383–389.

[336] A. Ishikawa, S. Motohashi, E. Ishikawa, et al., “A Phase I Study of Alpha-galactosylceramide (KRN7000)-pulsed Dendritic Cells in Patients With Advanced and Recurrent Non-small Cell Lung Cancer,” Clinical Cancer Research 11, no. 5 (2005): 1910–1917.

[337] T. Uchida, S. Horiguchi, Y. Tanaka, et al., “Phase I Study of Alpha-galactosylceramide-pulsed Antigen Presenting Cells Administration to the Nasal Submucosa in Unresectable or Recurrent Head and Neck Cancer,” Cancer Immunology, Immunotherapy 57, no. 3 (2008): 337–345.

[338] X. Li, M. Fujio, M. Imamura, et al., “Design of a Potent CD1d-binding NKT Cell Ligand as a Vaccine Adjuvant,” Proceedings of the National Academy of Sciences of the United States of America 107, no. 29 (2010): 13010–13015.

[339] S. Motohashi, A. Ishikawa, E. Ishikawa, et al., “A Phase I Study of in Vitro Expanded Natural Killer T Cells in Patients With Advanced and Recurrent Non-small Cell Lung Cancer,” Clinical Cancer Research 12, no. 20 Pt 1 (2006): 6079–6086.

[340] L. A. King, R. Lameris, T. D. de Gruijl, et al., “CD1d-Invariant Natural Killer T Cell-Based Cancer Immunotherapy: Alpha-Galactosylceramide and beyond,” Frontiers in Immunology 9 (2018): 1519.

[341] S. Inuki, N. Hirata, E. Kashiwabara, et al., “Polar Functional Group-containing Glycolipid CD1d Ligands Modulate Cytokine-biasing Responses and Prevent Experimental Colitis,” Scientific Reports 10, no. 1 (2020): 15766.

[342] C. Riillo, D. Caracciolo, K. Grillone, et al., “A Novel Bispecific T-Cell Engager (CD1a x CD3epsilon) BTCE Is Effective Against Cortical-Derived T Cell Acute Lymphoblastic Leukemia (T-ALL) Cells,” Cancers (Basel) 14, no. 12 (2022): 2886.

[343] D. Sanchez-Martinez, M. L. Baroni, F. Gutierrez-Aguera, et al., “Fratricide-resistant CD1a-specific CAR T Cells for the Treatment of Cortical T-cell Acute Lymphoblastic Leukemia,” Blood 133, no. 21 (2019): 2291–2304.

[344] Y. R. Li, Y. Zhou, J. Yu, et al., “Generation of Allogeneic CAR-NKT Cells From Hematopoietic Stem and Progenitor Cells Using a Clinically Guided Culture Method,” Nature Biotechnology 43, no. 3 (2025): 329–344.

[345] Y. Zhu, D. J. Smith, Y. Zhou, et al., “Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer,” Cell Stem Cell 25, no. 4 (2019): 542-557 e9.

[346] H. E. McWilliam, R. W. Birkinshaw, J. A. Villadangos, et al., “MR1 presentation of Vitamin B-based Metabolite Ligands,” Current Opinion in Immunology 34 (2015): 28–34.

[347] R. J. Napier, E. J. Adams, M. C. Gold, et al., “The Role of Mucosal Associated Invariant T Cells in Antimicrobial Immunity,” Frontiers in Immunology 6 (2015): 344.

[348] M. Lepore, A. Kalinichenko, S. Calogero, et al., “Functionally Diverse human T Cells Recognize Non-microbial Antigens Presented by MR1,” Elife 6 (2017): e24476.

[349] L. Mori, M. Lepore, and G. De Libero, “The Immunology of CD1- and MR1-Restricted T Cells,” Annual Review of Immunology 34 (2016): 479–510.

[350] A. J. Corbett, W. Awad, H. Wang, et al., “Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries,” Frontiers in Immunology 11 (2020): 1961.

[351] J. Lion, V. Debuysscher, A. Wlodarczyk, et al., “MR1B, a Natural Spliced Isoform of the MHC-related 1 Protein, Is Expressed as Homodimers at the Cell Surface and Activates MAIT Cells,” European Journal of Immunology 43, no. 5 (2013): 1363–1373.

[352] M. G. Constantinides, V. M. Link, S. Tamoutounour, et al., “MAIT Cells Are Imprinted by the Microbiota in Early Life and Promote Tissue Repair,” Science 366, no. 6464 (2019): eaax6624.

[353] J. Lopez-Sagaseta, C. L. Dulberger, J. E. Crooks, et al., “The Molecular Basis for Mucosal-Associated Invariant T Cell Recognition of MR1 Proteins,” Proceedings of the National Academy of Sciences of the United States of America 110, no. 19 (2013): E1771–E1778.

[354] H. E. G. McWilliam and J. A. Villadangos, “MR1 antigen Presentation to MAIT Cells and Other MR1-restricted T Cells,” Nature Reviews Immunology 24, no. 3 (2024): 178–192.

[355] P. Riegert, V. Wanner, and S. Bahram, “Genomics, Isoforms, Expression, and Phylogeny of the MHC Class I-related MR1 Gene,” Journal of Immunology 161, no. 8 (1998): 4066–4077.

[356] H. E. McWilliam, S. B. Eckle, A. Theodossis, et al., “The Intracellular Pathway for the Presentation of Vitamin B-related Antigens by the Antigen-presenting Molecule MR1,” Nature Immunology 17, no. 5 (2016): 531–537.

[357] G. A. Narayanan, A. Nellore, J. Tran, et al., “Alternative Splicing of MR1 Regulates Antigen Presentation to MAIT Cells,” Scientific Reports 10, no. 1 (2020): 15429.

[358] M. J. Harriff, E. Karamooz, A. Burr, et al., “Endosomal MR1 Trafficking Plays a Key Role in Presentation of Mycobacterium Tuberculosis Ligands to MAIT Cells,” Plos Pathogens 12, no. 3 (2016): e1005524.

[359] W. J. Chua, S. Kim, N. Myers, et al., “Endogenous MHC-related Protein 1 Is Transiently Expressed on the Plasma Membrane in a Conformation That Activates Mucosal-associated Invariant T Cells,” Journal of Immunology 186, no. 8 (2011): 4744–4750.

[360] H. E. McWilliam and J. A. Villadangos, “MR1 antigen Presentation to MAIT Cells: New Ligands, Diverse Pathways?,” Current Opinion in Immunology 52 (2018): 108–113.

[361] M. J. Miley, S. M. Truscott, Y. Y. Yu, et al., “Biochemical Features of the MHC-related Protein 1 Consistent With an Immunological Function,” Journal of Immunology 170, no. 12 (2003): 6090–6098.

[362] H. J. Lim, J. M. Wubben, C. P. Garcia, et al., “A Specialized Tyrosine-based Endocytosis Signal in MR1 Controls Antigen Presentation to MAIT Cells,” Journal of Cell Biology 221, no. 12 (2022): e202110125.

[363] R. Lamichhane and J. E. Ussher, “Expression and Trafficking of MR1,” Immunology 151, no. 3 (2017): 270–279.

[364] H. E. G. McWilliam and J. A. Villadangos, “How MR1 Presents a Pathogen Metabolic Signature to Mucosal-Associated Invariant T (MAIT) Cells,” Trends in Immunology 38, no. 9 (2017): 679–689.

[365] S. Huang, S. Gilfillan, S. Kim, et al., “MR1 uses an Endocytic Pathway to Activate Mucosal-associated Invariant T Cells,” Journal of Experimental Medicine 205, no. 5 (2008): 1201–1211.

[366] L. L. Bourhis, E. Martin, I. Péguillet, et al., “Antimicrobial Activity of Mucosal-associated Invariant T Cells,” Nature Immunology 11, no. 8 (2010): 701–708.

[367] K. Tsukamoto, J. E. Deakin, J. A. Graves, et al., “Exceptionally High Conservation of the MHC Class I-related Gene, MR1, Among Mammals,” Immunogenetics 65, no. 2 (2013): 115–124.

[368] S. Huang, E. Martin, S. Kim, et al., “MR1 antigen Presentation to Mucosal-associated Invariant T Cells Was Highly Conserved in Evolution,” Proceedings of the National Academy of Sciences of the United States of America 106, no. 20 (2009): 8290–8295.

[369] N. Goldfinch, P. Reinink, T. Connelley, et al., “Conservation of Mucosal Associated Invariant T (MAIT) Cells and the MR1 Restriction Element in Ruminants, and Abundance of MAIT Cells in Spleen,” Veterinary Research 41, no. 5 (2010): 62.

[370] A. Kurioka, J. E. Ussher, C. Cosgrove, et al., “MAIT Cells Are Licensed Through Granzyme Exchange to Kill Bacterially Sensitized Targets,” Mucosal Immunol 8, no. 2 (2015): 429–440.

[371] S. Marinovic, M. Lenartic, K. Mladenic, et al., “NKG2D-mediated Detection of Metabolically Stressed Hepatocytes by Innate-Like T Cells Is Essential for Initiation of NASH and Fibrosis,” Science Immunology 8, no. 87 (2023): eadd1599.

[372] R. Takasaki, E. Ito, M. Nagae, et al., “Development of Ribityllumazine Analogue as Mucosal-Associated Invariant T Cell Ligands,” Journal of the American Chemical Society 146, no. 43 (2024): 29964–29976.

[373] P. Georgel, M. Radosavljevic, C. Macquin, et al., “The Non-conventional MHC Class I MR1 Molecule Controls Infection by Klebsiella pneumoniae in Mice,” Molecular Immunology 48, no. 5 (2011): 769–775.

[374] W. J. Chua, S. M. Truscott, C. S. Eickhoff, et al., “Polyclonal Mucosa-associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection,” Infection and Immunity 80, no. 9 (2012): 3256–3267.

[375] D. T. Leung, T. R. Bhuiyan, N. S. Nishat, et al., “Circulating Mucosal Associated Invariant T Cells Are Activated in Vibrio cholerae O1 Infection and Associated With Lipopolysaccharide Antibody Responses,” PLOS Neglected Tropical Diseases 8, no. 8 (2014): e3076.

[376] L. Le Bourhis, M. Dusseaux, A. Bohineust, et al., “MAIT Cells Detect and Efficiently Lyse Bacterially-infected Epithelial Cells,” Plos Pathogens 9, no. 10 (2013): e1003681.

[377] Y. R. Li, K. Zhou, Y. Zhu, et al., “Breaking the Mold: Unconventional T Cells in Cancer Therapy,” Cancer Cell 43, no. 3 (2025): 317–322.

[378] J. Qu, B. Wu, L. Chen, et al., “CXCR6-positive Circulating Mucosal-associated Invariant T Cells Can Identify Patients With Non-small Cell Lung Cancer Responding to anti-PD-1 Immunotherapy,” Journal of Experimental & Clinical Cancer Research 43, no. 1 (2024): 134.

[379] Y. R. Li, J. Brown, Y. Yu, et al., “Targeting Immunosuppressive Tumor-Associated Macrophages Using Innate T Cells for Enhanced Antitumor Reactivity,” Cancers (Basel) 14, no. 11 (2022): 2749.

[380] Y. R. Li, K. Zhou, M. Wilson, et al., “Mucosal-associated Invariant T Cells for Cancer Immunotherapy,” Molecular Therapy 31, no. 3 (2023): 631–646.

[381] M. Yigit, O. F. Basoglu, and D. Unutmaz, “Mucosal-associated Invariant T Cells in Cancer: Dual Roles, Complex Interactions and Therapeutic Potential,” Frontiers in Immunology 15 (2024): 1369236.

[382] O. Rouxel, J. D. Silva, L. Beaudoin, et al., “Cytotoxic and Regulatory Roles of Mucosal-associated Invariant T Cells in Type 1 Diabetes,” Nature Immunology 18, no. 12 (2017): 1321–1331.

[383] G. Murayama, A. Chiba, H. Suzuki, et al., “A Critical Role for Mucosal-Associated Invariant T Cells as Regulators and Therapeutic Targets in Systemic Lupus Erythematosus,” Frontiers in Immunology 10 (2019): 2681.

[384] Q. Fan, H. Nan, Z. Li, et al., “New Insights Into MAIT Cells in Autoimmune Diseases,” Biomedicine & Pharmacotherapy 159 (2023): 114250.

[385] A. Chiba, G. Murayama, and S. Miyake, “Mucosal-Associated Invariant T Cells in Autoimmune Diseases,” Frontiers in Immunology 9 (2018): 1333.

[386] M. Kronenberg and T. Riffelmacher, “Defenders or Defectors: Mucosal-associated Invariant T Cells in Autoimmune Diseases,” Current Opinion in Immunology 93 (2025): 102542.

[387] M. C. Gold, R. J. Napier, and D. M. Lewinsohn, “MR1-restricted Mucosal Associated Invariant T (MAIT) Cells in the Immune Response to Mycobacterium tuberculosis,” Immunological Reviews 264, no. 1 (2015): 154–166.

[388] O. Jensen, S. Trivedi, K. Li, et al., “Use of a MAIT-Activating Ligand, 5-OP-RU, as a Mucosal Adjuvant in a Murine Model of Vibrio Cholerae O1 Vaccination,” Pathogens and Immunity 7, no. 1 (2022): 122–144.

[389] R. Rashu, M. Ninkov, C. M. Wardell, et al., “Targeting the MR1-MAIT Cell Axis Improves Vaccine Efficacy and Affords Protection Against Viral Pathogens,” Plos Pathogens 19, no. 6 (2023): e1011485.

[390] A. Amini, L. C. Garner, R. H. Shaw, et al., “MAIT and Other Innate-Like T Cells Integrate Adaptive Immune Responses to Modulate Interval-dependent Reactogenicity to mRNA Vaccines,” Science Immunology 10, no. 110 (2025): eadu3337.

[391] A. Amini, P. Klenerman, and N. M. Provine, “Role of Mucosal-associated Invariant T Cells in Coronavirus Disease 2019 Vaccine Immunogenicity,” Current Opinion in Virology 67 (2024): 101412.

[392] M. D. Crowther, G. Dolton, M. Legut, et al., “Genome-wide CRISPR-Cas9 Screening Reveals Ubiquitous T Cell Cancer Targeting via the Monomorphic MHC Class I-related Protein MR1,” Nature Immunology 21, no. 2 (2020): 178–185.

[393] G. Dolton, H. Thomas, L. R. Tan, et al., “MHC-related Protein 1-restricted Recognition of Cancer via a Semi-invariant TCR-alpha Chain,” Journal of Clinical Investigation 135, no. 1 (2025): e181895.

[394] T. V. Cornforth, N. Moyo, S. Cole, et al., “Conserved Allomorphs of MR1 Drive the Specificity of MR1-restricted TCRs,” Frontiers in Oncology 14 (2024): 1419528.

[395] Z. Wang, M. Wang, J. Chen, et al., “MR1-restricted T Cells: The New Dawn of Cancer Immunotherapy,” Bioscience Reports 40, no. 11 (2020): BSR20202962.

[396] P. Muthukutty, H. Y. Woo, M. Ragothaman, et al., “Recent Advances in Cancer Immunotherapy Delivery Modalities,” Pharmaceutics 15, no. 2 (2023): 504.

[397] S. P. Patel, T. Alonso-Gordoa, S. Banerjee, et al., “Phase 1/2 Study of Monalizumab plus durvalumab in Patients With Advanced Solid Tumors,” Journal for ImmunoTherapy of Cancer 12, no. 2 (2024): e007340.

[398] T. C. Hammond, M. A. Purbhoo, S. Kadel, et al., “A Phase 1/2 Clinical Trial of Invariant Natural Killer T Cell Therapy in Moderate-severe Acute respiratory Distress Syndrome,” Nature Communications 15, no. 1 (2024): 974.

[399] H. H. Xu, J. Gan, D. P. Xu, et al., “Comprehensive Transcriptomic Analysis Reveals the Role of the Immune Checkpoint HLA-G Molecule in Cancers,” Frontiers in Immunology 12 (2021): 614773.

[400] B. Salome, J. P. Sfakianos, D. Ranti, et al., “NKG2A and HLA-E Define an Alternative Immune Checkpoint Axis in Bladder Cancer,” Cancer Cell 40, no. 9 (2022): 1027–1043 e9.

[401] M. C. Chen, M. Y. Hung, C. M. Pan, et al., “Pemetrexed Combined With Dual Immune Checkpoint Blockade Enhances Cytotoxic T Lymphocytes Against Lung Cancer,” Cancer Science 114, no. 7 (2023): 2761–2773.

[402] N. Mamidi, M. Poellmann, K. Javius-Jones, et al., “Innovative Hydrogel-based Delivery Systems for Immunotherapy: A Review of Pre-clinical Progress,” Nano Research 17 (2024): 9031–9043.

[403] A. A. Celik, T. Kraemer, T. Huyton, et al., “The Diversity of the HLA-E-restricted Peptide Repertoire Explains the Immunological Impact of the Arg107Gly Mismatch,” Immunogenetics 68, no. 1 (2016): 29–41.

[404] T. Kraemer, A. A. Celik, T. Huyton, et al., “HLA-E: Presentation of a Broader Peptide Repertoire Impacts the Cellular Immune Response-Implications on HSCT Outcome,” Stem Cells International 2015 (2015): 346714.

[405] L. Kanevskiy, S. Erokhina, P. Kobyzeva, et al., “Dimorphism of HLA-E and Its Disease Association,” International Journal of Molecular Sciences 20, no. 21 (2019): 5496.

[406] S. Liu, N. A. Bos, E. A. M. Verschuuren, et al., “Biological Characteristics of HLA-G and Its Role in Solid Organ Transplantation,” Frontiers in Immunology 13 (2022): 902093.

[407] M. Milton and S. Mansour, “CD1-restricted T Cells: Are Unconventional Allies the Key to Future TB Vaccines?,” Frontiers in Immunology 16 (2025): 1629466.

[408] M. E. Huber, E. A. Larson, T. N. Lust, et al., “IFNgamma Regulates MR1 Transcription and Antigen Presentation,” Frontiers in Immunology 16 (2025): 1624767.

[409] C. Lima-Junior Jda and L. R. Pratt-Riccio, “Major Histocompatibility Complex and Malaria: Focus on Plasmodium Vivax Infection,” Frontiers in Immunology 7 (2016): 13.

RIGHTS & PERMISSIONS

2026 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.