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Cell Biology and Toxicology

, Volume 34, Issue 6, pp 441–457 | Cite as

History, applications, and challenges of immune repertoire research

  • Xiao Liu
  • Jinghua Wu
Review

Abstract

The diversity of T and B cells in terms of their receptor sequences is huge in the vertebrate’s immune system and provides broad protection against the vast diversity of pathogens. Immune repertoire is defined as the sum of T cell receptors and B cell receptors (also named immunoglobulin) that makes the organism’s adaptive immune system. Before the emergence of high-throughput sequencing, the studies on immune repertoire were limited by the underdeveloped methodologies, since it was impossible to capture the whole picture by the low-throughput tools. The massive paralleled sequencing technology suits perfectly the researches on immune repertoire. In this article, we review the history of immune repertoire studies, in terms of technologies and research applications. Particularly, we discuss several aspects of challenges in this field and highlight the efforts to develop potential solutions, in the era of high-throughput sequencing of the immune repertoire.

Keywords

Immune repertoire TCR BCR High-throughput sequencing 

Notes

Acknowledgements

We want to thank the supervision and guidance of Prof. Karsten Kristiansen from the University of Copenhagen and the support from BGI-Shenzhen for this work.

References

  1. Agathangelidis A, Darzentas N, Hadzidimitriou A, Brochet X, Murray F, Yan XJ, et al. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies. Blood. 2012;119:4467–75.Google Scholar
  2. Argaet VP, Schmidt CW, Burrows SR, Silins SL, Kurilla MG, Doolan DL, et al. Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus. J Exp Med. 1994;180:2335–40.Google Scholar
  3. Bashford-Rogers RJ, Palser AL, Huntly BJ, Rance R, Vassiliou GS, Follows GA, et al. Network properties derived from deep sequencing of human B-cell receptor repertoires delineate B-cell populations. Genome Res. 2013;23:1874–84.Google Scholar
  4. Bashford-Rogers RJ, Palser AL, Idris SF, Carter L, Epstein M, Callard RE, et al. Capturing needles in haystacks: a comparison of B-cell receptor sequencing methods. BMC Immunol. 2014;15:29.Google Scholar
  5. Bashford-Rogers RJ, Nicolaou KA, Bartram J, Goulden NJ, Loizou L, Koumas L, et al. Eye on the B-ALL: B-cell receptor repertoires reveal persistence of numerous B-lymphoblastic leukemia subclones from diagnosis to relapse. Leukemia. 2016;30:2312–21.Google Scholar
  6. Becattini S, Latorre D, Mele F, Foglierini M, De Gregorio C, Cassotta A, et al. T cell immunity. Functional heterogeneity of human memory CD4(+) T cell clones primed by pathogens or vaccines. Science. 2015;347:400–6.Google Scholar
  7. Benichou J, Ben-Hamo R, Louzoun Y, Efroni S. Rep-Seq: uncovering the immunological repertoire through next-generation sequencing. Immunology. 2012;135:183–91.Google Scholar
  8. Bolotin DA, Mamedov IZ, Britanova OV, Zvyagin IV, Shagin D, Ustyugova SV, et al. Next generation sequencing for TCR repertoire profiling: platform-specific features and correction algorithms. Eur J Immunol. 2012;42:3073–83.Google Scholar
  9. Bolotin DA, Shugay M, Mamedov IZ, Putintseva EV, Turchaninova MA, Zvyagin IV, et al. MiTCR: software for T-cell receptor sequencing data analysis. Nat Methods. 2013;10:813–4.Google Scholar
  10. Bolotin DA, Poslavsky S, Mitrophanov I, Shugay M, Mamedov IZ, Putintseva EV, et al. MiXCR: software for comprehensive adaptive immunity profiling. Nat Methods. 2015;12:380–1.Google Scholar
  11. Boyd SD, Marshall EL, Merker JD, Maniar JM, Zhang LN, Sahaf B, et al. Measurement and clinical monitoring of human lymphocyte clonality by massively parallel VDJ pyrosequencing. Sci Transl Med. 2009;1:12ra23.Google Scholar
  12. Britanova OV, Putintseva EV, Shugay M, Merzlyak EM, Turchaninova MA, Staroverov DB, et al. Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling. J Immunol. 2014;192:2689–98.Google Scholar
  13. Brochet X, Lefranc MP, Giudicelli V. IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucleic Acids Res. 2008;36:W503–8.Google Scholar
  14. Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJL, Furman D, et al. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015;160:37–47.Google Scholar
  15. Carlson CS, Emerson RO, Sherwood AM, Desmarais C, Chung MW, Parsons JM, et al. Using synthetic templates to design an unbiased multiplex PCR assay. Nat Commun. 2013;4:2680.Google Scholar
  16. Cha E, Klinger M, Hou Y, Cummings C, Ribas A, Faham M, et al. Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients. Sci Transl Med. 2014;6:238ra270.Google Scholar
  17. Cheung WC, Beausoleil SA, Zhang X, Sato S, Schieferl SM, Wieler JS, et al. A proteomics approach for the identification and cloning of monoclonal antibodies from serum. Nat Biotechnol. 2012;30:447–52.Google Scholar
  18. Chien YH, Meyer C, Bonneville M. Gammadelta T cells: first line of defense and beyond. Annu Rev Immunol. 2014;32:121–55.Google Scholar
  19. Dai K, He L, Khan SN, O'Dell S, McKee K, Tran K, et al. Rhesus macaque B-cell responses to an HIV-1 trimer vaccine revealed by unbiased longitudinal repertoire analysis. MBio. 2015;6.Google Scholar
  20. Dash P, Fiore-Gartland AJ, Hertz T, Wang GC, Sharma S, Souquette A, et al. Quantifiable predictive features define epitope-specific T cell receptor repertoires. Nature. 2017;547:89.Google Scholar
  21. DeKosky BJ, Ippolito GC, Deschner RP, Lavinder JJ, Wine Y, Rawlings BM, et al. High-throughput sequencing of the paired human immunoglobulin heavy and light chain repertoire. Nat Biotechnol. 2013;31:166–9.Google Scholar
  22. Egorov ES, Merzlyak EM, Shelenkov AA, Britanova OV, Sharonov GV, Staroverov DB, et al. Quantitative profiling of immune repertoires for minor lymphocyte counts using unique molecular identifiers. J Immunol. 2015;194:6155–63.Google Scholar
  23. Emerson RO, Sherwood AM, Rieder MJ, Guenthoer J, Williamson DW, Carlson CS, et al. High-throughput sequencing of T-cell receptors reveals a homogeneous repertoire of tumour-infiltrating lymphocytes in ovarian cancer. J Pathol. 2013;231:433–40.Google Scholar
  24. Emerson RO, DeWitt WS, Vignali M, Gravley J, Hu JK, Osborne EJ, et al. Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire. Nat Genet. 2017;49:659–65.Google Scholar
  25. Freeman JD, Warren RL, Webb JR, Nelson BH, Holt RA. Profiling the T-cell receptor beta-chain repertoire by massively parallel sequencing. Genome Res. 2009;19:1817–24.Google Scholar
  26. Gaeta BA, Malming HR, Jackson KJ, Bain ME, Wilson P, Collins AM. iHMMune-align: hidden Markov model-based alignment and identification of germline genes in rearranged immunoglobulin gene sequences. Bioinformatics. 2007;23:1580–7.Google Scholar
  27. Gao F, Wang K. Ligation-anchored PCR unveils immune repertoire of TCR-beta from whole blood. BMC Biotechnol. 2015;15:39.Google Scholar
  28. Garcia KC, Adams JJ, Feng D, Ely LK. The molecular basis of TCR germline bias for MHC is surprisingly simple. Nat Immunol. 2009;10:143–7.Google Scholar
  29. Gauss GH, Lieber MR. Mechanistic constraints on diversity in human V(D)J recombination. Mol Cell Biol. 1996;16:258–69.Google Scholar
  30. Gawad C, Pepin F, Carlton VE, Klinger M, Logan AC, Miklos DB, et al. Massive evolution of the immunoglobulin heavy chain locus in children with B precursor acute lymphoblastic leukemia. Blood. 2012;120:4407–17.Google Scholar
  31. Georgiou G, Ippolito GC, Beausang J, Busse CE, Wardemann H, Quake SR. The promise and challenge of high-throughput sequencing of the antibody repertoire. Nat Biotechnol. 2014;32:158–68.Google Scholar
  32. Gerlinger M, Quezada SA, Peggs KS, Furness AJ, Fisher R, Marafioti T, et al. Ultra-deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas. J Pathol. 2013;231:424–32.Google Scholar
  33. Germain RN. T-cell development and the CD4-CD8 lineage decision. Nat Rev Immunol. 2002;2:309–22.Google Scholar
  34. Glanville J, Kuo TC, von Budingen HC, Guey L, Berka J, Sundar PD, et al. Naive antibody gene-segment frequencies are heritable and unaltered by chronic lymphocyte ablation. Proc Natl Acad Sci U S A. 2011;108:20066–71.Google Scholar
  35. Glanville J, Huang H, Nau A, Hatton O, Wagar LE, Rubelt F, et al. Identifying specificity groups in the T cell receptor repertoire. Nature. 2017.Google Scholar
  36. Gorski J, Yassai M, Zhu X, Kissela B, Kissella B, Keever C, et al. Circulating T cell repertoire complexity in normal individuals and bone marrow recipients analyzed by CDR3 size spectratyping. Correlation with immune status. J Immunol. 1994;152:5109–19.Google Scholar
  37. Greiff V, Bhat P, Cook SC, Menzel U, Kang W, Reddy ST. A bioinformatic framework for immune repertoire diversity profiling enables detection of immunological status. Genome Med. 2015a;7:49.Google Scholar
  38. Greiff V, Miho E, Menzel U, Reddy ST. Bioinformatic and statistical analysis of adaptive immune repertoires. Trends Immunol. 2015b;36:738–49.Google Scholar
  39. Greiff V, Menzel U, Miho E, Weber C, Riedel R, Cook S, et al. Systems analysis reveals high genetic and antigen-driven predetermination of antibody repertoires throughout B cell development. Cell Rep. 2017a;19:1467–78.Google Scholar
  40. Greiff V, Weber CR, Palme J, Bodenhofer U, Miho E, Menzel U, et al. Learning the high-dimensional immunogenomic features that predict public and private antibody repertoires. J Immunol. 2017b;199:2985–97.Google Scholar
  41. Han A, Glanville J, Hansmann L, Davis MM. Linking T-cell receptor sequence to functional phenotype at the single-cell level. Nat Biotechnol. 2014;32:684–92.Google Scholar
  42. Harden JL, Hamm D, Gulati N, Lowes MA, Krueger JG. Deep sequencing of the T-cell receptor repertoire demonstrates polyclonal T-cell infiltrates in psoriasis. F1000Res. 2015;4:460.Google Scholar
  43. He J, Wu J, Jiao Y, Wagner-Johnston N, Ambinder RF, Diaz LA Jr, et al. IgH gene rearrangements as plasma biomarkers in non-Hodgkin's lymphoma patients. Oncotarget. 2011;2:178–85.Google Scholar
  44. Heather JM, Best K, Oakes T, Gray ER, Roe JK, Thomas N, et al. Dynamic perturbations of the T-cell receptor repertoire in chronic HIV infection and following antiretroviral therapy. Front Immunol. 2015;6:644.Google Scholar
  45. Hindley JP, Ferreira C, Jones E, Lauder SN, Ladell K, Wynn KK, et al. Analysis of the T-cell receptor repertoires of tumor-infiltrating conventional and regulatory T cells reveals no evidence for conversion in carcinogen-induced tumors. Cancer Res. 2011;71:736–46.Google Scholar
  46. Howie B, Sherwood AM, Berkebile AD, Berka J, Emerson RO, Williamson DW, et al. High-throughput pairing of T cell receptor alpha and beta sequences. Sci Transl Med. 2015;7:301ra131.Google Scholar
  47. Jackson KJ, Liu Y, Roskin KM, Glanville J, Hoh RA, Seo K, et al. Human responses to influenza vaccination show seroconversion signatures and convergent antibody rearrangements. Cell Host Microbe. 2014;16:105–14.Google Scholar
  48. Jiang N, Weinstein JA, Penland L, White RA, Fisher DS, Quake SR. Determinism and stochasticity during maturation of the zebrafish antibody repertoire. Proc Natl Acad Sci. 2011;108:5348–53.Google Scholar
  49. Jiang N, He J, Weinstein JA, Penland L, Sasaki S, He XS, et al. Lineage structure of the human antibody repertoire in response to influenza vaccination. Sci Transl Med. 2013;5:171ra119.Google Scholar
  50. Khan N, Cobbold M, Keenan R, Moss PA. Comparative analysis of CD8+ T cell responses against human cytomegalovirus proteins pp65 and immediate early 1 shows similarities in precursor frequency, oligoclonality, and phenotype. J Infect Dis. 2002;185:1025–34.Google Scholar
  51. Khan TA, Friedensohn S, Gorter de Vries AR, Straszewski J, Ruscheweyh HJ, Reddy ST. Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting. Sci Adv. 2016;2:e1501371.Google Scholar
  52. Kinde I, Wu J, Papadopoulos N, Kinzler KW, Vogelstein B. Detection and quantification of rare mutations with massively parallel sequencing. Proc Natl Acad Sci U S A. 2011;108:9530–5.Google Scholar
  53. Klarenbeek PL, Tak PP, van Schaik BD, Zwinderman AH, Jakobs ME, Zhang Z, et al. Human T-cell memory consists mainly of unexpanded clones. Immunol Lett. 2010;133:42–8.Google Scholar
  54. Kleinstein SH, Louzoun Y, Shlomchik MJ. Estimating hypermutation rates from clonal tree data. J Immunol. 2003;171:4639–49.Google Scholar
  55. Klinger M, Pepin F, Wilkins J, Asbury T, Wittkop T, Zheng J, et al. Multiplex identification of antigen-specific T cell receptors using a combination of immune assays and immune receptor sequencing. PLoS One. 2015;10:e0141561.Google Scholar
  56. Koch U, Radtke F. Mechanisms of T cell development and transformation. Annu Rev Cell Dev Biol. 2011;27:539–62.Google Scholar
  57. Kurtz DM, Green MR, Bratman SV, Scherer F, Liu CL, Kunder CA, et al. Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing. Blood. 2015;125:3679–87.Google Scholar
  58. Larson ED, Maizels N. Transcription-coupled mutagenesis by the DNA deaminase AID. Genome Biol. 2004;5:211.Google Scholar
  59. Laserson U, Vigneault F, Gadala-Maria D, Yaari G, Uduman M, Vander Heiden JA, et al. High-resolution antibody dynamics of vaccine-induced immune responses. Proc Natl Acad Sci U S A. 2014;111:4928–33.Google Scholar
  60. Lathrop SK, Bloom SM, Rao SM, Nutsch K, Lio CW, Santacruz N, et al. Peripheral education of the immune system by colonic commensal microbiota. Nature. 2011;478:250–4.Google Scholar
  61. Laydon DJ, Melamed A, Sim A, Gillet NA, Sim K, Darko S, et al. Quantification of HTLV-1 clonality and TCR diversity. PLoS Comput Biol. 2014;10:e1003646.Google Scholar
  62. Li Z, Woo CJ, Iglesias-Ussel MD, Ronai D, Scharff MD. The generation of antibody diversity through somatic hypermutation and class switch recombination. Genes Dev. 2004;18:1–11.Google Scholar
  63. Li S, Lefranc MP, Miles JJ, Alamyar E, Giudicelli V, Duroux P, et al. IMGT/HighV QUEST paradigm for T cell receptor IMGT clonotype diversity and next generation repertoire immunoprofiling. Nat Commun. 2013;4:2333.Google Scholar
  64. Li X, Duan X, Yang K, Zhang W, Zhang C, Fu L, et al. Comparative analysis of immune repertoires between Bactrian Camel's conventional and heavy-chain antibodies. PLoS One. 2016;11:e0161801.Google Scholar
  65. Liu X, Zhang W, Zeng X, Zhang R, Du Y, Hong X, et al. Systematic comparative evaluation of methods for investigating the TCRbeta repertoire. PLoS One. 2016;11:e0152464.Google Scholar
  66. Logan AC, Gao H, Wang C, Sahaf B, Jones CD, Marshall EL, et al. High-throughput VDJ sequencing for quantification of minimal residual disease in chronic lymphocytic leukemia and immune reconstitution assessment. Proc Natl Acad Sci U S A. 2011;108:21194–9.Google Scholar
  67. Logan AC, Vashi N, Faham M, Carlton V, Kong K, Buno I, et al. Immunoglobulin and T cell receptor gene high-throughput sequencing quantifies minimal residual disease in acute lymphoblastic leukemia and predicts post-transplantation relapse and survival. Biol Blood Marrow Transplant. 2014;20:1307–13.Google Scholar
  68. Looney TJ, Lee JY, Roskin KM, Hoh RA, King J, Glanville J, et al. Human B-cell isotype switching origins of IgE. J Allergy Clin Immunol. 2015.Google Scholar
  69. Luo W, Ma L, Wen Q, Wang N, Zhou MQ, Wang XN. Analysis of the interindividual conservation of T cell receptor alpha- and beta-chain variable regions gene in the peripheral blood of patients with systemic lupus erythematosus. Clin Exp Immunol. 2008;154:316–24.Google Scholar
  70. Madi A, Shifrut E, Reich-Zeliger S, Gal H, Best K, Ndifon W, et al. T-cell receptor repertoires share a restricted set of public and abundant CDR3 sequences that are associated with self-related immunity. Genome Res. 2014;24:1603–12.Google Scholar
  71. Mamedov IZ, Britanova OV, Zvyagin IV, Turchaninova MA, Bolotin DA, Putintseva EV, et al. Preparing unbiased T-cell receptor and antibody cDNA libraries for the deep next generation sequencing profiling. Front Immunol. 2013;4:456.Google Scholar
  72. McInerney P, Adams P, Hadi MZ. Error rate comparison during polymerase chain reaction by DNA polymerase. Mol Biol Int. 2014;2014:287430.Google Scholar
  73. McLean-Tooke A, Barge D, Spickett GP, Gennery AR. T cell receptor Vbeta repertoire of T lymphocytes and T regulatory cells by flow cytometric analysis in healthy children. Clin Exp Immunol. 2008;151:190–8.Google Scholar
  74. Meng W, Zhang B, Schwartz GW, Rosenfeld AM, Ren D, Thome JJC, et al. An atlas of B-cell clonal distribution in the human body. Nat Biotechnol. 2017;35:879.Google Scholar
  75. Miles JJ, Douek DC, Price DA. Bias in the alphabeta T-cell repertoire: implications for disease pathogenesis and vaccination. Immunol Cell Biol. 2011;89:375–87.Google Scholar
  76. Moss PA, Moots RJ, Rosenberg WM, Rowland-Jones SJ, Bodmer HC, McMichael AJ, et al. Extensive conservation of alpha and beta chains of the human T-cell antigen receptor recognizing HLA-A2 and influenza A matrix peptide. Proc Natl Acad Sci U S A. 1991;88:8987–90.Google Scholar
  77. Muraro PA, Robins H, Malhotra S, Howell M, Phippard D, Desmarais C, et al. T cell repertoire following autologous stem cell transplantation for multiple sclerosis. J Clin Invest. 2014;124:1168–72.Google Scholar
  78. Nezlin R. Combinatorial events in generation of antibody diversity. Comb Chem High Throughput Screen. 2001;4:377–83.Google Scholar
  79. Nguyen P, Ma J, Pei D, Obert C, Cheng C, Geiger TL. Identification of errors introduced during high throughput sequencing of the T cell receptor repertoire. BMC Genomics. 2011;12:106.Google Scholar
  80. Oksenberg JR, Panzara MA, Begovich AB, Mitchell D, Erlich HA, Murray RS, et al. Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis. Nature. 1993;362:68–70.Google Scholar
  81. Pacholczyk R, Ignatowicz H, Kraj P, Ignatowicz L. Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells. Immunity. 2006;25:249–59.Google Scholar
  82. Pannetier C, Cochet M, Darche S, Casrouge A, Zoller M, Kourilsky P. 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 U S A. 1993;90:4319–23.Google Scholar
  83. Peters DG, Kassam AB, Yonas H, O'Hare EH, Ferrell RE, Brufsky AM. Comprehensive transcript analysis in small quantities of mRNA by SAGE-lite. Nucleic Acids Res. 1999;27:e39.Google Scholar
  84. Prabakaran P, Streaker E, Chen W, Dimitrov DS. 454 antibody sequencing—error characterization and correction. BMC Res Notes. 2011;4:404.Google Scholar
  85. Price DA, Brenchley JM, Ruff LE, Betts MR, Hill BJ, Roederer M, et al. Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses. J Exp Med. 2005;202:1349–61.Google Scholar
  86. Pui CH, Pei D, Coustan-Smith E, Jeha S, Cheng C, Bowman WP, et al. Clinical utility of sequential minimal residual disease measurements in the context of risk-based therapy in childhood acute lymphoblastic leukaemia: a prospective study. Lancet Oncol. 2015;16:465–74.Google Scholar
  87. Pulsipher MA, Carlson C, Langholz B, Wall DA, Schultz KR, Bunin N, et al. IgH-V(D)J NGS-MRD measurement pre- and early post-allotransplant defines very low- and very high-risk ALL patients. Blood. 2015;125:3501–8.Google Scholar
  88. Reddy ST, Ge X, Miklos AE, Hughes RA, Kang SH, Hoi KH, et al. Monoclonal antibodies isolated without screening by analyzing the variable-gene repertoire of plasma cells. Nat Biotechnol. 2010;28:965–9.Google Scholar
  89. Robert L, Tsoi J, Wang X, Emerson R, Homet B, Chodon T, et al. CTLA4 blockade broadens the peripheral T-cell receptor repertoire. Clin Cancer Res. 2014;20:2424–32.Google Scholar
  90. Robins H. Immunosequencing: applications of immune repertoire deep sequencing. Curr Opin Immunol. 2013;25:646–52.Google Scholar
  91. Roschewski M, Dunleavy K, Pittaluga S, Moorhead M, Pepin F, Kong K, et al. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. Lancet Oncol. 2015;16:541–9.Google Scholar
  92. Rose DR. The generation of antibody diversity. Am J Hematol. 1982;13:91–9.Google Scholar
  93. Rothenberg EV, Moore JE, Yui MA. Launching the T-cell-lineage developmental programme. Nat Rev Immunol. 2008;8:9–21.Google Scholar
  94. Sainz-Perez A, Lim A, Lemercier B, Leclerc C. The T-cell receptor repertoire of tumor-infiltrating regulatory T lymphocytes is skewed toward public sequences. Cancer Res. 2012;72:3557–69.Google Scholar
  95. Schatz DG, Swanson PC. V(D)J recombination: mechanisms of initiation. Annu Rev Genet. 2011;45:167–202.Google Scholar
  96. Schroeder HW Jr. Similarity and divergence in the development and expression of the mouse and human antibody repertoires. Dev Comp Immunol. 2006;30:119–35.Google Scholar
  97. Shugay M, Britanova OV, Merzlyak EM, Turchaninova MA, Mamedov IZ, Tuganbaev TR, et al. Towards error-free profiling of immune repertoires. Nat Methods. 2014;11:653–5.Google Scholar
  98. Shugay M, Bagaev DV, Zvyagin IV, Vroomans RM, Crawford JC, Dolton G, et al. VDJdb: a curated database of T-cell receptor sequences with known antigen specificity. Nucleic Acids Res. 2017:gkx760–0.Google Scholar
  99. Silverman GJ, Goodyear CS. Confounding B-cell defences: lessons from a staphylococcal superantigen. Nat Rev Immunol. 2006;6:465–75.Google Scholar
  100. Sing GK, Li D, Chen X, Macnaughton T, Lichanska AM, Butterworth L, et al. A molecular comparison of T lymphocyte populations infiltrating the liver and circulating in the blood of patients with chronic hepatitis B: evidence for antigen-driven selection of a public complementarity-determining region 3 (CDR3) motif. Hepatology. 2001;33:1288–98.Google Scholar
  101. Six A, Mariotti-Ferrandiz ME, Chaara W, Magadan S, Pham HP, Lefranc MP, et al. The past, present, and future of immune repertoire biology—the rise of next-generation repertoire analysis. Front Immunol. 2013;4:413.Google Scholar
  102. Stern JN, Yaari G, Vander Heiden JA, Church G, Donahue WF, Hintzen RQ, et al. B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Sci Transl Med. 2014;6:248ra107.Google Scholar
  103. Sui W, Hou X, Zou G, Che W, Yang M, Zheng C, et al. Composition and variation analysis of the TCR beta-chain CDR3 repertoire in systemic lupus erythematosus using high-throughput sequencing. Mol Immunol. 2015;67:455–64.Google Scholar
  104. Sundling C, Li Y, Huynh N, Poulsen C, Wilson R, O'Dell S, et al. High-resolution definition of vaccine-elicited B cell responses against the HIV primary receptor binding site. Sci Transl Med. 2012;4:142ra196.Google Scholar
  105. Teng G, Papavasiliou FN. Immunoglobulin somatic hypermutation. Annu Rev Genet. 2007;41:107–20.Google Scholar
  106. Thapa DR, Tonikian R, Sun C, Liu M, Dearth A, Petri M, et al. Longitudinal analysis of peripheral blood T cell receptor diversity in patients with systemic lupus erythematosus by next-generation sequencing. Arthritis Res Ther. 2015;17:132.Google Scholar
  107. Thomas N, Heather J, Ndifon W, Shawe-Taylor J, Chain B. Decombinator: a tool for fast, efficient gene assignment in T-cell receptor sequences using a finite state machine. Bioinformatics. 2013;29:542–50.Google Scholar
  108. Tickotsky N, Sagiv T, Prilusky J, Shifrut E, Friedman N. McPAS-TCR: a manually curated catalogue of pathology-associated T cell receptor sequences. Bioinformatics. 2017;33:2924–9.Google Scholar
  109. Tipton CM, Fucile CF, Darce J, Chida A, Ichikawa T, Gregoretti I, et al. Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus. Nat Immunol. 2015;16:755–65.Google Scholar
  110. Trepel F. Number and distribution of lymphocytes in man. A critical analysis. Klin Wochenschr. 1974;52:511–5.Google Scholar
  111. Turchaninova MA, Britanova OV, Bolotin DA, Shugay M, Putintseva EV, Staroverov DB, et al. Pairing of T-cell receptor chains via emulsion PCR. Eur J Immunol. 2013;43:2507–15.Google Scholar
  112. Turchaninova MA, Davydov A, Britanova OV, Shugay M, Bikos V, Egorov ES, et al. High-quality full-length immunoglobulin profiling with unique molecular barcoding. Nat Protoc. 2016;11:1599–616.Google Scholar
  113. Umemura T, Yoshizawa K, Ota M, Katsuyama Y, Inada H, Tanaka E, et al. Analysis of T cell repertoire in the liver of patients with chronic hepatitis C. Clin Exp Immunol. 2000;121:120–6.Google Scholar
  114. van den Beemd R, Boor PP, van Lochem EG, Hop WC, Langerak AW, Wolvers-Tettero IL, et al. Flow cytometric analysis of the Vbeta repertoire in healthy controls. Cytometry. 2000;40:336–45.Google Scholar
  115. van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 concerted action BMH4-CT98-3936. Leukemia. 2003;17:2257–317.Google Scholar
  116. Vander Heiden JA, Yaari G, Uduman M, Stern JN, O'Connor KC, Hafler DA, et al. pRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires. Bioinformatics. 2014;30:1930–2.Google Scholar
  117. Vollmers C, Sit RV, Weinstein JA, Dekker CL, Quake SR. Genetic measurement of memory B-cell recall using antibody repertoire sequencing. Proc Natl Acad Sci U S A. 2013;110:13463–8.Google Scholar
  118. von Budingen HC, Kuo TC, Sirota M, van Belle CJ, Apeltsin L, Glanville J, et al. B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest. 2012;122:4533–43.Google Scholar
  119. Wang C, Sanders CM, Yang Q, Schroeder HW Jr, Wang E, Babrzadeh F, et al. High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets. Proc Natl Acad Sci U S A. 2010;107:1518–23.Google Scholar
  120. Wang C, Liu Y, Cavanagh MM, Le Saux S, Qi Q, Roskin KM, et al. B-cell repertoire responses to varicella-zoster vaccination in human identical twins. Proc Natl Acad Sci U S A. 2015;112:500–5.Google Scholar
  121. Wang T, Wang C, Wu J, He C, Zhang W, Liu J, et al. The different T-cell receptor repertoires in breast cancer tumors, draining lymph nodes, and adjacent tissues. Cancer Immunol Res. 2017;5:148–56.Google Scholar
  122. Warren RL, Freeman JD, Zeng T, Choe G, Munro S, Moore R, et al. 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 Res. 2011;21:790–7.Google Scholar
  123. Weinstein JA, Jiang N, White RA 3rd, Fisher DS, Quake SR. High-throughput sequencing of the zebrafish antibody repertoire. Science. 2009;324:807–10.Google Scholar
  124. Weng WK, Armstrong R, Arai S, Desmarais C, Hoppe R, Kim YH. Minimal residual disease monitoring with high-throughput sequencing of T cell receptors in cutaneous T cell lymphoma. Sci Transl Med. 2013;5:214ra171.Google Scholar
  125. Wiley SR, Raman VS, Desbien A, Bailor HR, Bhardwaj R, Shakri AR, et al. Targeting TLRs expands the antibody repertoire in response to a malaria vaccine. Sci Transl Med. 2011;3:93ra69.Google Scholar
  126. Wu D, Sherwood A, Fromm JR, Winter SS, Dunsmore KP, Loh ML, et al. High-throughput sequencing detects minimal residual disease in acute T lymphoblastic leukemia. Sci Transl Med. 2012;4:134ra163.Google Scholar
  127. Wu J, Jia S, Wang C, Zhang W, Liu S, Zeng X, et al. Minimal residual disease detection and evolved IGH clones analysis in acute B lymphoblastic leukemia using IGH deep sequencing. Front Immunol. 2016;7:403.Google Scholar
  128. Wucherpfennig KW, Ota K, Endo N, Seidman JG, Rosenzweig A, Weiner HL, et al. Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein. Science. 1990;248:1016–9.Google Scholar
  129. Yaari G, Kleinstein SH. Practical guidelines for B-cell receptor repertoire sequencing analysis. Genome Med. 2015;7:121.Google Scholar
  130. Ye J, Ma N, Madden TL, Ostell JM. IgBLAST: an immunoglobulin variable domain sequence analysis tool. Nucleic Acids Res. 2013;41:W34–40.Google Scholar
  131. Yu XG, Lichterfeld M, Chetty S, Williams KL, Mui SK, Miura T, et al. Mutually exclusive T-cell receptor induction and differential susceptibility to human immunodeficiency virus type 1 mutational escape associated with a two-amino-acid difference between HLA class I subtypes. J Virol. 2007;81:1619–31.Google Scholar
  132. Zhang W, Du Y, Su Z, Wang C, Zeng X, Zhang R, et al. IMonitor: a robust pipeline for TCR and BCR repertoire analysis. Genetics. 2015;201:459–72.Google Scholar
  133. Zvyagin IV, Pogorelyy MV, Ivanova ME, Komech EA, Shugay M, Bolotin DA, et al. Distinctive properties of identical twins' TCR repertoires revealed by high-throughput sequencing. Proc Natl Acad Sci U S A. 2014;111:5980–5.Google Scholar

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© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.BGI-ShenzhenShenzhenChina

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