The impact of SARS-CoV-2 peptides on activation of NK cells

Abstract

BACKGROUND: NK cells, alone with T lymphocytes, have a high antiviral activity. Exploring the contribution of NK cells in fighting SARS-CoV-2 infection may promote the development of appropriate treatments for COVID-19. Previously, NK cell response was considered nonspecific, provided by a combination of signals from activating and inhibitory receptors. Currently, the existence of certain subpopulations of antigen-specific, or adaptive, NK cells has been shown.

AIM: To evaluate the functional response of NK cells induced by SARS-CoV-2 peptides.

MATERIALS AND METHODS: The functional response of NK cells to SARS-CoV-2 peptides was determined by their degranulation (surface CD107a expression) and IFNγ production levels, and by the activation degree (HLA-DR expression level). Volunteers who recovered from COVID-19 participated in the study, and immune cells from a healthy volunteer without SARS-CoV-2-specific antibodies were used as controls.

RESULTS: NK cells from individuals who had recovered from COVID-19, in contrast to a donor who had not been infected, showed a higher level of IFNγ production in response to SARS-CoV-2 peptides, compared with control samples. The level of degranulation of NK cells from donors previously infected with SARS-CoV-2 was higher than in the corresponding control. The proportion of activated NK cells obtained from recovered donors was also higher in samples stimulated with SARS-CoV-2 peptides.

CONCLUSIONS: We have demonstrated the activation of NK cells obtained from people who had previously recovered from COVID-19 in response to SARS-CoV-2 peptide antigens in cultures of peripheral mononuclear cells in vitro. This study reveals the possibility for further investigation of antigen-specific NK cells in COVID-19 disease. The use of such cells could help develop treatments for SARS-CoV-2 infection.

Keywords

immunology / NK cells / SARS-CoV-2 / IFNγ / degranulation of NK cells / antigen-specificity

References

[1] Sivori S, Vacca P, Del Zotto G, et al. Human NK cells: surface receptors, inhibitory checkpoints, and translational applications. Cell Mol Immunol. 2019;16(5):430–441. DOI: 10.1038/s41423-019-0206-4

[2] Sivori S., Vacca P., Del Zotto G. et al. Human NK cells: surface receptors, inhibitory checkpoints, and translational applications // Cell. Mol. Immunol. 2019. Vol. 16, No. 5. P. 430–441. DOI: 10.1038/s41423-019-0206-4

[3] Paust S, von Andrian UH. Natural killer cell memory. Nat Immunol. 2011;12(6):500–508. DOI: 10.1038/ni.2032

[4] Paust S., von Andrian U.H. Natural killer cell memory // Nat. Immunol. 2011. Vol. 12, No. 6. P. 500–508. DOI: 10.1038/ni.2032

[5] Gumá M, Budt M, Sáez A, et al. Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts. Blood. 2006;107(9):3624–3631. DOI: 10.1182/BLOOD-2005-09-3682

[6] Gumá M., Budt M., Sáez A. et al. Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts // Blood. 2006. Vol. 107, No. 9. P. 3624–3631. DOI: 10.1182/BLOOD-2005-09-3682

[7] Hammer Q, Rückert T, Borst EM, et al. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells article. Nat Immunol. 2018;19:453–463. DOI: 10.1038/S41590-018-0082-6

[8] Hammer Q., Rückert T., Borst E.M. et al. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells article // Nat. Immunol. 2018. Vol. 19. P. 453–463. DOI: 10.1038/S41590-018-0082-6

[9] Kovalenko EI, Streltsova MA, Kanevskiy LM, et al. Identification of human memory-like NK cells. Curr Protoc Cytom. 2017;79:9.50.1–9.50.11. DOI: 10.1002/CPCY.13

[10] Kovalenko E.I., Streltsova M.A., Kanevskiy L.M. et al. Identification of human memory-like NK cells // Curr. Protoc. Cytom. 2017. Vol. 79. P. 9.50.1–9.50.11. DOI: 10.1002/CPCY.13

[11] Wijaya RS, Read SA, Truong NR, et al. HBV vaccination and HBV infection induces HBV-specific natural killer cell memory. Gut. 2021;70(2):357–369. DOI: 10.1136/GUTJNL-2019-319252

[12] Wijaya R.S., Read S.A., Truong N.R. et al. HBV vaccination and HBV infection induces HBV-specific natural killer cell memory // Gut. 2021. Vol. 70, No. 2. P. 357–369. DOI: 10.1136/GUTJNL-2019-319252

[13] Maucourant C, Filipovic I, Ponzetta A, et al. Natural killer cell immunotypes related to COVID-19 disease severity. Sci Immunol. 2020;5(50):eabd6832. DOI: 10.1126/SCIIMMUNOL.ABD6832

[14] Maucourant C., Filipovic I., Ponzetta A. et al. Natural killer cell immunotypes related to COVID-19 disease severity // Sci. Immunol. 2020. Vol. 5, No. 50. P. eabd6832. DOI: 10.1126/SCIIMMUNOL.ABD6832

RIGHTS & PERMISSIONS

Eco-Vector