The shape of the lymphocyte receptor repertoire: Lessons from the B cell receptor

Frontiers in Immunology

Volumn 4, Issue SEP, 2013, Pages

  Jackson, Katherine J L ^a   Kidd, Marie J ^a   Wang, Yan ^a   Collins, Andrew M ^a  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

Author keywords

BCR repertoire; Combinatorial diversity; Junctional diversity; Private clonotypes; Public clonotypes; TCR repertoire; V(D)J recombination

Indexed keywords

EID: 84885979012     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2013.00263     Document Type: Review

References (110)

1. Tonegawa S. Somatic generation of antibody diversity. Nature (1983) 302:575-81. doi:10.1038/302575a0.
2. Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol (2010) 125:S41-52. doi:10.1016/j.jaci.2009.09.046.
3. Davis MM, Bjorkman PJ. T-cell antigen receptor genes and T-cell recognition. Nature (1988) 334:395-402. doi:10.1038/334395a0.
4. Takihara Y, Tkachuk D, Michalopoulos E, Champagne E, Reimann J, Minden M, et al. 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 A (1988) 85:6097-101. doi:10.1073/pnas.85.16.6097.
5. Nikolich-Zugich J, Slifka MK, Messaoudi I. The many important facets of T-cell repertoire diversity. Nat Rev Immunol (2004) 4:123-32. doi:10.1038/nri1292.
6. Desiderio SV, Yancopoulos GD, Paskind M, Thomas E, Boss MA, Landau N, et al. Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature (1984) 311:752-5.
7. Davies JM, Platts-Mills TA, Aalberse RC. The enigma of IgE+ B-cell memory in human subjects. J Allergy Clin Immunol (2013) 131:972-6. doi:10.1016/j.jaci.2012.12.1569.
8. Fukui K, Noma T, Takeuchi K, Kobayashi N, Hatanaka M, Honjo T. Origin of adult T-cell leukemia virus. Implication for its zoonosis. Mol Biol Med (1983) 1:447-56.
9. Watson CT, Breden F. The immunoglobulin heavy chain locus: genetic variation, missing data, and implications for human disease. Genes Immun (2012) 13:363-73. doi:10.1038/gene.2012.12.
10. Rada C, Milstein C. The intrinsic hypermutability of antibody heavy and light chain genes decays exponentially. EMBO J (2001) 20:4570-6. doi:10.1093/emboj/20.16.4570.
11. Odegard VH, Schatz DG. Targeting of somatic hypermutation. Nat Rev Immunol (2006) 6:573-83. doi:10.1038/nri1896.
12. Pallares N, Lefebvre S, Contet V, Matsuda F, Lefranc MP. The human immunoglobulin heavy variable genes. Exp Clin Immunogenet (1999) 16:36-60. doi:10.1159/000019095.
13. Ohm-Laursen L, Larsen SR, Barington T. Identification of two new alleles, IGHV3-23*04 and IGHJ6*04, and the complete sequence of the IGHV3-h pseudogene in the human immunoglobulin locus and their prevalences in Danish Caucasians. Immunogenetics (2005) 57:621-7. doi:10.1007/s00251-005-0035-8.
14. Romo-Gonzalez T, Morales-Montor J, Rodriguez-Dorantes M, Vargas-Madrazo E. Novel substitution polymorphisms of human immunoglobulin VH genes in Mexicans. Hum Immunol (2005) 66:732-40. doi:10.1016/j.humimm.2005.03.002.
15. Wang Y, Jackson KJ, Sewell WA, Collins AM. Many human immunoglobulin heavy-chain IGHV gene polymorphisms have been reported in error. Immunol Cell Biol (2008) 86:111-5.
16. Wang Y, Jackson KJ, Gaeta B, Pomat W, Siba P, Sewell WA, et al. Genomic screening by 454 pyrosequencing identifies a new human IGHV gene and sixteen other new IGHV allelic variants. Immunogenetics (2011) 63:259-65. doi:10.1007/s00251-010-0510-8.
17. Watson CT, Steinberg KM, Huddleston J, Warren RL, Malig M, Schein J, et al. Complete haplotype sequence of the human immunoglobulin heavy-chain variable, diversity, and joining genes and characterization of allelic and copy-number variation. Am J Hum Genet (2013) 92:530-46. doi:10.1016/j.ajhg.2013.03.004.
18. Boyd SD, Gaeta BA, Jackson KJ, Fire AZ, Marshall EL, Merker JD, et al. Individual variation in the germline Ig gene repertoire inferred from variable region gene rearrangements. J Immunol (2010) 184:6986-92. doi:10.4049/jimmunol.1000445.
19. Kidd MJ, Chen Z, Wang Y, Jackson KJ, Zhang L, Boyd SD, et al. The inference of phased haplotypes for the immunoglobulin H chain V region gene loci by analysis of VDJ gene rearrangements. J Immunol (2012) 188:1333-40. doi:10.4049/jimmunol.1102097.
20. Collins AM, Wang Y, Singh V, Yu P, Jackson KJ, Sewell WA. The reported germline repertoire of human immunoglobulin kappa chain genes is relatively complete and accurate. Immunogenetics (2008) 60:669-76. doi:10.1007/s00251-008-0325-z.
21. Feeney AJ, Atkinson MJ, Cowan MJ, Escuro G, Lugo G. A defective Vkappa A2 allele in Navajos which may play a role in increased susceptibility to Haemophilus influenzae type b disease. J Clin Invest (1996) 97:2277-82. doi:10.1172/JCI118669.
22. Rowen L, Koop BF, Hood L. The complete 685-kilobase DNA sequence of the human beta T cell receptor locus. Science (1996) 272:1755-62. doi:10.1126/science.272.5269.1755.
23. Boysen C, Simon MI, Hood L. Analysis of the 1.1-Mb human alpha/delta T-cell receptor locus with bacterial artificial chromosome clones. Genome Res (1997) 7:330-8.
24. Ibberson MR, Copier JP, Llop E, Navarrete C, Hill AV, Cruickshank JK, et al. T-cell receptor variable alpha (TCRAV) polymorphisms in European, Chinese, South American, AfroCaribbean, and Gambian populations. Immunogenetics (1998) 47:124-30. doi:10.1007/s002510050337.
25. Moody AM, Reyburn H, Willcox N, Newsom-Davis J. New polymorphism of the human T-cell receptor AV28S1 gene segment. Immunogenetics (1998) 48:62-4. doi:10.1007/s002510050401.
26. Subrahmanyan L, Eberle MA, Clark AG, Kruglyak L, Nickerson DA. Sequence variation and linkage disequilibrium in the human T-cell receptor beta (TCRB) locus. Am J Hum Genet (2001) 69:381-95. doi:10.1086/321297.
27. Mackelprang R, Livingston RJ, Eberle MA, Carlson CS, Yi Q, Akey JM, et al. Sequence diversity, natural selection and linkage disequilibrium in the human T cell receptor alpha/delta locus. Hum Genet (2006) 119:255-66. doi:10.1007/s00439-005-0111-z.
28. Vessey SJ, Bell JI, Jakobsen BK. A functionally significant allelic polymorphism in a T cell receptor V beta gene segment. Eur J Immunol (1996) 26:1660-3. doi:10.1002/eji.1830260739.
29. Gras S, Chen Z, Miles JJ, Liu YC, Bell MJ, Sullivan LC, et al. Allelic polymorphism in the T cell receptor and its impact on immune responses. J Exp Med (2010) 207:1555-67. doi:10.1084/jem.20100603.
30. Corbett SJ, Tomlinson IM, Sonnhammer EL, Buck D, Winter G. Sequence of the human immunoglobulin diversity (D) segment locus: a systematic analysis provides no evidence for the use of DIR segments, inverted D segments, "minor" D segments or D-D recombination. J Mol Biol (1997) 270:587-97. doi:10.1006/jmbi.1997.1141.
31. Munshaw S, Kepler TB. SoDA2: a Hidden Markov Model approach for identification of immunoglobulin rearrangements. Bioinformatics (2010) 26:867-72. doi:10.1093/bioinformatics/btq056.
32. Ye J, Ma N, Madden TL, Ostell JM. IgBLAST: an immunoglobulin variable domain sequence analysis tool. Nucleic Acids Res (2013). doi:10.1093/nar/gkt382.
33. 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. doi:10.1093/bioinformatics/btm147.
34. Jackson KJ, Boyd S, Gaeta BA, Collins AM. Benchmarking the performance of human antibody gene alignment utilities using a 454 sequence dataset. Bioinformatics (2010) 26:3129-30. doi:10.1093/bioinformatics/btq604.
35. Basu M, Hegde MV, Modak MJ. Synthesis of compositionally unique DNA by terminal deoxynucleotidyl transferase. Biochem Biophys Res Commun (1983) 111:1105-12. doi:10.1016/0006-291X(83)91413-4.
36. Gauss GH, Lieber MR. Mechanistic constraints on diversity in human V(D)J recombination. Mol Cell Biol (1996) 16:258-69.
37. Jackson KJ, Gaeta BA, Collins AM. Identifying highly mutated IGHD genes in the junctions of rearranged human immunoglobulin heavy chain genes. J Immunol Methods (2007) 324:26-37. doi:10.1016/j.jim.2007.04.011.
38. 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. doi:10.1093/bioinformatics/btt004.
39. Lee CE, Jackson KJ, Sewell WA, Collins AM. Use of IGHJ and IGHD gene mutations in analysis of immunoglobulin sequences for the prognosis of chronic lymphocytic leukemia. Leuk Res (2007) 31:1247-52. doi:10.1016/j.leukres.2006.10.013.
40. Ndifon W, Gal H, Shifrut E, Aharoni R, Yissachar N, Waysbort N, et al. Chromatin conformation governs T-cell receptor Jbeta gene segment usage. Proc Natl Acad Sci U S A (2012) 109:15865-70. doi:10.1073/pnas.1203916109.
41. Quiros Roldan E, Sottini A, Bettinardi A, Albertini A, Imberti L, Primi D. Different TCRBV genes generate biased patterns of V-D-J diversity in human T cells. Immunogenetics (1995) 41:91-100.
42. Livak F, Burtrum DB, Rowen L, Schatz DG, Petrie HT. Genetic modulation of T cell receptor gene segment usage during somatic recombination. J Exp Med (2000) 192:1191-6. doi:10.1084/jem.192.8.1191.
43. 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. doi:10.1101/gr.115428.110.
44. 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. doi:10.1038/sj.leu.2403202.
45. Matthews C, Catherwood M, Morris TC, Alexander HD. Routine analysis of IgVH mutational status in CLL patients using BIOMED-2 standardized primers and protocols. Leuk Lymphoma (2004) 45:1899-904. doi:10.1080/10428190410001710812.
46. Glanville J, Kuo TC, Von Büdingen H-C, 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. doi:10.1073/pnas.1107498108.
47. Briney BS, Willis JR, Mckinney BA, Crowe Jr JE. High-throughput antibody sequencing reveals genetic evidence of global regulation of the naive and memory repertoires that extends across individuals. Genes Immun (2012) 13:469-73. doi:10.1038/gene.2012.20.
48. Benichou J, Glanville J, Prak ET, Azran R, Kuo TC, Pons J, et al. The restricted DH gene reading frame usage in the expressed human antibody repertoire is selected based upon its amino acid content. J Immunol (2013) 190:5567-77. doi:10.4049/jimmunol.1201929.
49. Yamada M, Wasserman R, Reichard BA, Shane S, Caton AJ, Rovera G. Preferential utilization of specific immunoglobulin heavy chain diversity and joining segments in adult human peripheral blood B lymphocytes. J Exp Med (1991) 173:395-407. doi:10.1084/jem.173.2.395.
50. Volpe JM, Kepler TB. Large-scale analysis of human heavy chain V(D)J recombination patterns. Immunome Res (2008) 4:3. doi:10.1186/1745-7580-4-3.
51. Klein R, Jaenichen R, Zachau HG. Expressed human immunoglobulin kappa genes and their hypermutation. Eur J Immunol (1993) 23:3248-62. doi:10.1002/eji.1830231231.
52. Cox JP, Tomlinson IM, Winter G. A directory of human germ-line V kappa segments reveals a strong bias in their usage. Eur J Immunol (1994) 24:827-36. doi:10.1002/eji.1830240409.
53. Weber JC, Blaison G, Martin T, Knapp AM, Pasquali JL. Evidence that the V kappa III gene usage is nonstochastic in both adult and newborn peripheral B cells and that peripheral CD5+ adult B cells are oligoclonal. J Clin Invest (1994) 93:2093-105. doi:10.1172/JCI117204.
54. Foster SJ, Brezinschek HP, Brezinschek RI, Lipsky PE. Molecular mechanisms and selective influences that shape the kappa gene repertoire of IgM+ B cells. J Clin Invest (1997) 99:1614-27. doi:10.1172/JCI119324.
55. Jackson KJ, Wang Y, Gaeta BA, Pomat W, Siba P, Rimmer J, et al. Divergent human populations show extensive shared IGK rearrangements in peripheral blood B cells. Immunogenetics (2012) 64:3-14. doi:10.1007/s00251-011-0559-z.
56. Gay D, Saunders T, Camper S, Weigert M. Receptor editing: an approach by autoreactive B cells to escape tolerance. J Exp Med (1993) 177:999-1008. doi:10.1084/jem.177.4.999.
57. Tiegs SL, Russell DM, Nemazee D. Receptor editing in self-reactive bone marrow B cells. J Exp Med (1993) 177:1009-20. doi:10.1084/jem.177.4.1009.
58. Mehr R, Shannon M, Litwin S. Models for antigen receptor gene rearrangement. I. Biased receptor editing in B cells: implications for allelic exclusion. J Immunol (1999) 163:1793-8.
59. Ignatovich O, Tomlinson IM, Jones PT, Winter G. The creation of diversity in the human immunoglobulin V(lambda) repertoire. J Mol Biol (1997) 268:69-77. doi:10.1006/jmbi.1997.0956.
60. Vasicek TJ, Leder P. Structure and expression of the human immunoglobulin lambda genes. J Exp Med (1990) 172:609-20. doi:10.1084/jem.172.2.609.
61. Farner NL, Dorner T, Lipsky PE. Molecular mechanisms and selection influence the generation of the human V lambda J lambda repertoire. J Immunol (1999) 162:2137-45.
62. Tuaillon N, Taylor LD, Lonberg N, Tucker PW, Capra JD. Human immunoglobulin heavy-chain minilocus recombination in transgenic mice: gene-segment use in mu and gamma transcripts Proc Natl Acad Sci U S A (1993) 90:3720-4. doi:10.1073/pnas.90.8.3720.
63. Hoi KH, Ippolito GC. Intrinsic bias and public rearrangements in the human immunoglobulin Vlambda light chain repertoire. Genes Immun (2013) 14:271-6. doi:10.1038/gene.2013.10.
64. Craddock TP, Zumla AM, Ollier WE, Chintu CZ, Muyinda GP, Lancaster FC, et al. Predominance of one T-cell antigen receptor BV haplotype in African populations. Immunogenetics (2000) 51:231-7. doi:10.1007/s002510050036.
65. Donaldson IJ, Shefta J, Lawson CA, Bushnell JR, Morgan AW, Isaacs JD, et al. Unique TCR beta-subunit variable gene haplotypes in Africans. Immunogenetics (2002) 53:884-93. doi:10.1007/s00251-001-0406-8.
66. McMurry MT, Hernandez-Munain C, Lauzurica P, Krangel MS. Enhancer control of local accessibility to V(D)J recombinase. Mol Cell Biol (1997) 17:4553-61.
67. Nadel B, Tang A, Escuro G, Lugo G, Feeney AJ. Sequence of the spacer in the recombination signal sequence affects V(D)J rearrangement frequency and correlates with nonrandom Vkappa usage in vivo. J Exp Med (1998) 187:1495-503. doi:10.1084/jem.187.9.1495.
68. Feeney AJ, Tang A, Ogwaro KM. B-cell repertoire formation: role of the recombination signal sequence in non-random V segment utilization. Immunol Rev (2000) 175:59-69. doi:10.1111/j.1600-065X.2000.imr017508.x.
69. Posnett DN, Vissinga CS, Pambuccian C, Wei S, Robinson MA, Kostyu D, et al. Level of human TCRBV3S1 (V beta 3) expression correlates with allelic polymorphism in the spacer region of the recombination signal sequence. J Exp Med (1994) 179:1707-11. doi:10.1084/jem.179.5.1707.
70. Wei Z, Lieber MR. Lymphoid V(D)J recombination. Functional analysis of the spacer sequence within the recombination signal. J Biol Chem (1993) 268:3180-3.
71. Matsuda F, Ishii K, Bourvagnet P, Kuma K, Hayashida H, Miyata T, et al. The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus. J Exp Med (1998) 188:2151-62. doi:10.1084/jem.188.11.2151.
72. Sasso EH, Willems Van Dijk K, Bull A, Van Der Maarel SM, Milner EC. VH genes in tandem array comprise a repeated germline motif. J Immunol (1992) 149:1230-6.
73. Sasso EH, Johnson T, Kipps TJ. Expression of the immunoglobulin VH gene 51p1 is proportional to its germline gene copy number. J Clin Invest (1996) 97:2074-80. doi:10.1172/JCI118644.
74. Souto-Carneiro MM, Longo NS, Russ DE, Sun HW, Lipsky PE. Characterization of the human Ig heavy chain antigen binding complementarity determining region 3 using a newly developed software algorithm, JOINSOLVER. J Immunol (2004) 172:6790-802.
75. 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. doi:10.1126/scitranslmed.3000540.
76. De Preval C, Fougereau M. Specific interaction between VH and VL regions of human monoclonal immunoglobulins. J Mol Biol (1976) 102:657-78. doi:10.1016/0022-2836(76)90340-5.
77. Brezinschek HP, Foster SJ, Dorner T, Brezinschek RI, Lipsky PE. Pairing of variable heavy and variable kappa chains in individual naive and memory B cells. J Immunol (1998) 160:4762-7.
78. de Wildt RM, Hoet RM, Van Venrooij WJ, Tomlinson IM, Winter G. Analysis of heavy and light chain pairings indicates that receptor editing shapes the human antibody repertoire. J Mol Biol (1999) 285:895-901. doi:10.1006/jmbi.1998.2396.
79. 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. doi:10.1038/nbt.2492.
80. Arnaout R, Lee W, Cahill P, Honan T, Sparrow T, Weiand M, et al. High-resolution description of antibody heavy-chain repertoires in humans. PLoS ONE (2011) 6:e22365. doi:10.1371/journal.pone.0022365.
81. Roth DB, Menetski JP, Nakajima PB, Bosma MJ, Gellert M. V(D)J recombination: broken DNA molecules with covalently sealed (hairpin) coding ends in scid mouse thymocytes. Cell (1992) 70:983-91. doi:10.1016/0092-8674(92)90248-B.
82. Lafaille JJ, Decloux A, Bonneville M, Takagaki Y, Tonegawa S. Junctional sequences of T cell receptor gamma delta genes: implications for gamma delta T cell lineages and for a novel intermediate of V-(D)-J joining. Cell (1989) 59:859-70. doi:10.1016/0092-8674(89)90609-0.
83. Tian C, Luskin GK, Dischert KM, Higginbotham JN, Shepherd BE, Crowe Jr JE. Evidence for preferential Ig gene usage and differential TdT and exonuclease activities in human naive and memory B cells. Mol Immunol (2007) 44:2173-83. doi:10.1016/j.molimm.2006.11.020.
84. Jackson KJ, Gaeta B, Sewell W, Collins AM. Exonuclease activity and P nucleotide addition in the generation of the expressed immunoglobulin repertoire. BMC Immunol (2004) 5:19. doi:10.1186/1471-2172-5-19.
85. Lu H, Schwarz K, Lieber MR. Extent to which hairpin opening by the Artemis:DNA-PKcs complex can contribute to junctional diversity in V(D)J recombination. Nucleic Acids Res (2007) 35:6917-23. doi:10.1093/nar/gkm823.
86. Cabaniols JP, Fazilleau N, Casrouge A, Kourilsky P, Kanellopoulos JM. Most alpha/beta T cell receptor diversity is due to terminal deoxynucleotidyl transferase. J Exp Med (2001) 194:1385-90. doi:10.1084/jem.194.9.1385.
87. Murugan A, Mora T, Walczak AM, Callan CG. Statistical inference of the generation probability of T-cell receptors from sequence repertoires. Proc Natl Acad Sci USA (2012) 109:16161-6. doi:10.1073/pnas.1212755109.
88. Hofle M, Linthicum DS, Ioerger T. Analysis of diversity of nucleotide and amino acid distributions in the VD and DJ joining regions in Ig heavy chains. Mol Immunol (2000) 37:827-35. doi:10.1016/S0161-5890(00)00110-3.
89. Boubnov NV, Wills ZP, Weaver DT. V(D)J recombination coding junction formation without DNA homology: processing of coding termini. Mol Cell Biol (1993) 13:6957-68.
90. Nadel B, Feeney AJ. Influence of coding-end sequence on coding-end processing in V(D)J recombination. J Immunol (1995) 155:4322-9.
91. Saada R, Weinberger M, Shahaf G, Mehr R. Models for antigen receptor gene rearrangement: CDR3 length. Immunol Cell Biol (2007) 85:323-32. doi:10.1038/sj.icb.7100055.
92. 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. doi:10.1182/blood-2011-11-393694.
93. Hoogeboom R, Van Kessel KP, Hochstenbach F, Wormhoudt TA, Reinten RJ, Wagner K, et al. A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi. J Exp Med (2013) 210:59-70. doi:10.1084/jem.20121801.
94. Smith K, Garman L, Wrammert J, Zheng NY, Capra JD, Ahmed R, et al. Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen. Nat Protoc (2009) 4:372-84. doi:10.1038/nprot.2009.3.
95. 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. doi:10.1126/scitranslmed.3004794.
96. Wu YC, Kipling D, Dunn-Walters DK. Age-related changes in human peripheral blood IGH repertoire following vaccination. Front Immunol (2012) 3:193. doi:10.3389/fimmu.2012.00193.
97. Wu X, Zhou T, Zhu J, Zhang B, Georgiev I, Wang C, et al. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science (2011) 333:1593-602. doi:10.1126/science.1207532.
98. Parameswaran P, Yi Liu Q, Roskin KM, Jackson KK, Dixit VP, Lee J-Y, et al. Coherent immune repertoire signatures in human dengue. Cell Host Microbe (Forthcoming 2013).
99. 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. doi:10.1073/pnas.88.20.8987.
100. 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. doi:10.1084/jem.180.6.2335.
101. Pannetier C, Even J, Kourilsky P. T-cell repertoire diversity and clonal expansions in normal and clinical samples. Immunol Today (1995) 16:176-81. doi:10.1016/0167-5699(95)80117-0.
102. Altman JD, Moss PA, Goulder PJ, Barouch DH, Mcheyzer-Williams MG, Bell JI, et al. Phenotypic analysis of antigen-specific T lymphocytes. Science (1996) 274:94-6. doi:10.1126/science.274.5284.94.
103. Garrido P, Ruiz-Cabello F, Barcena P, Sandberg Y, Canton J, Lima M, et al. Monoclonal TCR-Vbeta13.1+/CD4+/NKa+/CD8-/+dim T-LGL lymphocytosis: evidence for an antigen-driven chronic T-cell stimulation origin. Blood (2007) 109:4890-8. doi:10.1182/blood-2006-05-022277.
104. Crompton L, Khan N, Khanna R, Nayak L, Moss PA. CD4+ T cells specific for glycoprotein B from cytomegalovirus exhibit extreme conservation of T-cell receptor usage between different individuals. Blood (2008) 111:2053-61. doi:10.1182/blood-2007-04-079863.
105. Moon JJ, Chu HH, Pepper M, Mcsorley SJ, Jameson SC, Kedl RM, et al. Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity (2007) 27:203-13. doi:10.1016/j.immuni.2007.07.007.
106. Alanio C, Lemaitre F, Law HK, Hasan M, Albert ML. Enumeration of human antigen-specific naive CD8+ T cells reveals conserved precursor frequencies. Blood (2010) 115:3718-25. doi:10.1182/blood-2009-10-251124.
107. Kwok WW, Tan V, Gillette L, Littell CT, Soltis MA, Lafond RB, et al. Frequency of epitope-specific naive CD4(+) T cells correlates with immunodominance in the human memory repertoire. J Immunol (2012) 188:2537-44. doi:10.4049/jimmunol.1102190.
108. Venturi V, Kedzierska K, Price DA, Doherty PC, Douek DC, Turner SJ, et al. Sharing of T cell receptors in antigen-specific responses is driven by convergent recombination. Proc Natl Acad Sci USA (2006) 103:18691-6. doi:10.1073/pnas.0608907103.
109. Quigley MF, Greenaway HY, Venturi V, Lindsay R, Quinn KM, Seder RA, et al. Convergent recombination shapes the clonotypic landscape of the naive T-cell repertoire. Proc Natl Acad Sci USA (2010) 107:19414-9. doi:10.1073/pnas.1010586107.
110. 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. doi:10.1038/icb.2010.139.