Characterization of human αβTCR repertoire and discovery of D-D fusion in TCRβ chains
Peipei Liu, Di Liu, Xi Yang, Jing Gao, Yan Chen, Xue Xiao, Fei Liu, Jing Zou, Jun Wu, Juncai Ma, Fangqing Zhao, Xuyu Zhou, George F. Gao, Baoli Zhu
Characterization of human αβTCR repertoire and discovery of D-D fusion in TCRβ chains
The characterization of the human T-cell receptor (TCR) repertoire has made remarkable progress, with most of the work focusing on the TCRβ chains. Here, we analyzed the diversity and complexity of both the TCRα and TCRβ repertoires of three healthy donors. We found that the diversity of the TCRα repertoire is higher than that of the TCRβ repertoire, whereas the usages of the V and J genes tended to be preferential with similar TRAV and TRAJ patterns in all three donors. The V-J pairings, like the V and J gene usages, were slightly preferential. We also found that the TRDV1 gene rearranges with the majority of TRAJ genes, suggesting that TRDV1 is a shared TRAV/DV gene (TRAV42/DV1). Moreover, we uncovered the presence of tandem TRBD (TRB D gene) usage in ∼2% of the productive human TCRβ CDR3 sequences.
TCR repertoire / next-generation sequencing / V/J usage / V-J pairing / CDR3 / D-D fusion
[1] |
Arstila TP, Casrouge A, Baron V, Even J, Kanellopoulos J, Kourilsky P(1999) A direct estimate of the human alphabeta T cell receptor diversity. Science286: 958-961
CrossRef
Google scholar
|
[2] |
Bank I, Book M, Cohen L, Kneller A, Rosental E, Pras M, Bassat IB, Ben-Nun A (1992) Expansion of a unique subpopulation of cytotoxic T cells that express a C alpha V delta 1 T-cell receptor gene in a patient with severe persistent neutropenia. Blood80: 3157-3163
|
[3] |
Bank I, Cohen L, Kneller A, de Rosbo NK, Book M, Ben-Nun A (2003) Aberrant T-Cell Receptor Signalling of Interferon-γ- and Tumour Necrosis Factor-α-Producing Cytotoxic CD8+Vδ1/Vβ16 T Cells in a Patient with Chronic Neutropenia. Scand J Immunol58: 89-98
CrossRef
Google scholar
|
[4] |
Bassing CH, Swat W, Alt FW(2002) The mechanism and regulation of chromosomal V(D)J recombination. Cell109(Suppl): S45-S55
CrossRef
Google scholar
|
[5] |
Borgulya P, Kishi H, Uematsu Y, von Boehmer H (1992) Exclusion and inclusion of alpha and beta Tcell receptor alleles. Cell69: 529-537
CrossRef
Google scholar
|
[6] |
Castelli C, Mazzocchi A, Salvi S, Anichini A, Sensi M(1992) Use of the V delta 1 variable region in the functional T-cell receptor alpha chain of a WT31+ cytotoxic T lymphocyte clone which speciflcally recognizes HLA-A2 molecule. Scand J Immunol35: 487-494
CrossRef
Google scholar
|
[7] |
Freeman JD, Warren RL, Webb JR, Nelson BH, Holt RA(2009) Proflling the T-cell receptor beta-chain repertoire by massively parallel sequencing. Genome Res19: 1817-1824
CrossRef
Google scholar
|
[8] |
Fuschiotti P, Pasqual N, Hierle V, Borel E, London J, Marche PN, Jouvin-Marche E (2007) Analysis of the TCR alpha-chain rearrangement proflle in human T lymphocytes. Mol Immunol44: 3380-3388
CrossRef
Google scholar
|
[9] |
Genolet R, Stevenson BJ, Farinelli L, Osteras M, Luescher IF(2012) Highly diverse TCRalpha chain repertoire of pre-immune CD8(+) T cells reveals new insights in gene recombination. EMBO J31: 1666-1678
CrossRef
Google scholar
|
[10] |
Gorski J, Yassai M, Zhu X, Kissela B, Kissella B, Keever C, Flomenberg N(1994) Circulating T cell repertoire complexity in normal individuals and bone marrow recipients analyzed by CDR3 size spectratyping. Correlation with immune status. J Immunol152: 5109-5119
|
[11] |
Hempel WM, Stanhope-Baker P, Mathieu N, Huang F, Schlissel MS, Ferrier P(1998) Enhancer control of V(D)Jrecombination at the TCRβ locus: differential effects on DNA cleavage and joining. Genes & Development12: 2305-2317
CrossRef
Google scholar
|
[12] |
Huang C, Kanagawa O(2001) Ordered and coordinated rearrangement of the TCR alpha locus: role of secondary rearrangement in thymic selection. J Immunol166: 2597-2601
CrossRef
Google scholar
|
[13] |
Klarenbeek PL, Tak PP, van Schaik BD, Zwinderman AH, Jakobs ME, Zhang Z, van Kampen AH, van Lier RA, Baas F, de Vries N (2010) Human T-cell memory consists mainly of unexpanded clones. Immunol Lett133: 42-48
CrossRef
Google scholar
|
[14] |
Klarenbeek PL, Remmerswaal EB, ten Berge IJ, Doorenspleet ME, van Schaik BD, Esveldt RE, Koch SD, ten Brinke A, van Kampen AH, Bemelman FJ
CrossRef
Google scholar
|
[15] |
Krangel MS(2009) Mechanics of T cell receptor gene rearrangement. Curr Opin Immunol21: 133-139
CrossRef
Google scholar
|
[16] |
Larimore K, McCormick MW, Robins HS, Greenberg PD(2012) Shaping of human germline IgH repertoires revealed by deep sequencing. J Immunol189: 3221-3230
CrossRef
Google scholar
|
[17] |
Lefranc MP(2001) Nomenclature of the human T cell receptor genes. Curr Protoc Immunol Appendix 1, Appendix 1O Lefranc MP (2011) From IMGT-ONTOLOGY CLASSIFICATION Axiom to IMGT standardized gene and allele nomenclature: for immunoglobulins (IG) and Tcell receptors (TR). Cold Spring Harb Protoc2011: 627-632
|
[18] |
Lefranc MP, Rabbitts TH(1990) Genetic organization of the human T-cell receptor gamma and delta loci. Res Immunol141: 565-577
CrossRef
Google scholar
|
[19] |
Li H, Ye C, Ji G, Wu X, Xiang Z, Li Y, Cao Y, Liu X, Douek DC, Price DA
CrossRef
Google scholar
|
[20] |
Loh EY, Cwirla S, Seraflni AT, Phillips JH, Lanier LL(1988) Human T-cell-receptor delta chain: genomic organization, diversity, and expression in populations of cells. Proc Natl Acad Sci USA85: 9714-9718
CrossRef
Google scholar
|
[21] |
Mardis ER(2008) Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet9: 387-402
CrossRef
Google scholar
|
[22] |
Meek KD, Hasemann CA, Capra JD(1989) Novel rearrangements at the immunoglobulin D locus. Inversions and fusions add to IgH somatic diversity. J Exp Med170: 39-57
CrossRef
Google scholar
|
[23] |
Miossec C(1990) Further analysis of the T cell receptor gamma/ delta+ peripheral lymphocyte subset. The V delta 1 gene segment is expressed with either C alpha or C delta. J Exp Med171: 1171-1188
CrossRef
Google scholar
|
[24] |
Miossec C, Caignard A, Ferradini L, Roman-Roman S, Faure F, Michalaki H, Triebel F, Hercend T(1991) Molecular characterization of human T cell receptor alpha chains including a V delta 1-encoded variable segment. Eur J Immunol21: 1061-1064
CrossRef
Google scholar
|
[25] |
Murphy KM, Travers P, Walport M(2007) Janeway’s Immunobiology. UK, Garland Science, London
|
[26] |
Neller MA, Burrows JM, Rist MJ, Miles JJ, Burrows SR(2013) High frequency of herpesvirus-speciflc clonotypes in the human T cell repertoire can remain stable over decades with minimal turnover. J Virol87: 697-700
CrossRef
Google scholar
|
[27] |
Nikolich-Zugich J, Slifka MK, Messaoudi I(2004) The many important facets of T-cell repertoire diversity. Nat Rev Immunol4: 123-132
CrossRef
Google scholar
|
[28] |
Olaru A, Petrie HT, Livak F(2005) Beyond the 12/23 rule of VDJ recombination independent of the Rag proteins. J Immunol174: 6220-6226
CrossRef
Google scholar
|
[29] |
Ozawa T, Kishi H, Muraguchi A(2006) Ampliflcation and analysis of cDNA generated from a single cell by 5′-RACE: application to isolation of antibody heavy and light chain variable gene sequences from single B cells. Biotechniques40: 469-478
CrossRef
Google scholar
|
[30] |
Padovan E, Casorati G, Dellabona P, Meyer S, Brockhaus M, Lanzavecchia A(1993) Expression of two T cell receptor alpha chains: dual receptor T cells. Science262: 422-424
CrossRef
Google scholar
|
[31] |
Pannetier C, Cochet M, Darche S, Casrouge A, Zoller M, Kourilsky P(1993) The Sizes of the Cdr3 Hypervariable Regions of the Murine T-Cell Receptor Beta-Chains Vary as a Function of the Recombined Germ-Line Segments. Proc Natl Acad Sci USA90: 4319-4323
CrossRef
Google scholar
|
[32] |
Pasqual N, Gallagher M, Aude-Garcia C, Loiodice M, Thuderoz F, Demongeot J, Ceredig R, Marche PN, Jouvin-Marche E (2002) Quantitative and Qualitative Changes in V-J Rearrangements During Mouse Thymocytes Differentiation: Implication For a Limited T Cell Receptor Chain Repertoire. J Exp Med196: 1163-1174
CrossRef
Google scholar
|
[33] |
Quigley MF, Greenaway HY, Venturi V, Lindsay R, Quinn KM, Seder RA, Douek DC, Davenport MP, Price DA(2010) Convergent recombination shapes the clonotypic landscape of the naïve T-cell repertoire. Proc Natl Acad Sci U S A107: 19414-19419
CrossRef
Google scholar
|
[34] |
Robins HS, Campregher PV, Srivastava SK, Wacher A, Turtle CJ, Kahsai O, Riddell SR, Warren EH, Carlson CS(2009) Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood114: 4099-4107
CrossRef
Google scholar
|
[35] |
Robins HS, Srivastava SK, Campregher PV, Turtle CJ, Andriesen J, Riddell SR, Carlson CS, Warren EH(2010) Overlap and effective size of the human CD8+ Tcell receptor repertoire. Sci Transl Med2, 47ra64
|
[36] |
Roth ME, Holman PO, Kranz DM(1991) Nonrandom use of J alpha gene segments. Influence of V alpha and J alpha gene location. J Immunol147: 1075-1081
|
[37] |
Ryu CJ, Haines BB, Draganov DD, Kang YH, Whitehurst CE, Schmidt T, Hong HJ, Chen J(2003) The T cell receptor beta enhancer promotes access and pairing of Dbeta and Jbeta gene segments during V(D)J recombination. Proc Natl Acad Sci USA100: 13465-13470
CrossRef
Google scholar
|
[38] |
Shendure J, Ji H(2008) Next-generation DNA sequencing. Nat Biotechnol26: 1135-1145
CrossRef
Google scholar
|
[39] |
Sherwood AM, Desmarais C, Livingston RJ, Andriesen J, Haussler M, Carlson CS, Robins H(2011). Deep sequencing of the human TCRgamma and TCRbeta repertoires suggests that TCRbeta rearranges after alphabeta and gammadelta T cell commitment. Sci Transl Med3, 90ra61
|
[40] |
Takihara Y, Tkachuk D, Michalopoulos E, Champagne E, Reimann J, Minden M, Mak TW(1988) Sequence and organization of the diversity, joining, and constant region genes of the human T-cell delta-chain locus. Proc Natl Acad Sci U S A85: 6097-6101
CrossRef
Google scholar
|
[41] |
Ueno T, Tomiyama H, Fujiwara M, Oka S, Takiguchi M(2003) HLA class I-restricted recognition of an HIV-derived epitope peptide by a human T cell receptor alpha chain having a Vdelta1 variable segment. Eur J Immunol33: 2910-2916
CrossRef
Google scholar
|
[42] |
Venturi V, Quigley MF, Greenaway HY, Ng PC, Ende ZS, McIntosh T, Asher TE, Almeida JR, Levy S, Price DA
CrossRef
Google scholar
|
[43] |
Wang C, Sanders CM, Yang Q, Schroeder HW Jr, Wang E, Babrzadeh F, Gharizadeh B, Myers RM, Hudson JR Jr, Davis RW
CrossRef
Google scholar
|
[44] |
Warren RL, Freeman JD, Zeng T, Choe G, Munro S, Moore R, Webb JR, Holt RA(2011) Exhaustive T-cell repertoire sequencing of human peripheral blood samples reveals signatures of antigen selection and a directly measured repertoire size of at least 1 million clonotypes. Genome Res21: 790-797
CrossRef
Google scholar
|
[45] |
Yousfl Monod M, Giudicelli V, Chaume D, Lefranc MP(2004) IMGT/ JunctionAnalysis: the flrst tool for the analysis of the immunoglobulin and T cell receptor complex V-J and V-D-J JUNCTIONs. Bioinformatics20(Suppl 1): i379-i385
CrossRef
Google scholar
|
/
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