Understanding the drivers of MHC restriction of T cell receptors

Nature Reviews Immunology

Volumn 18, Issue 7, 2018, Pages 467-478

  La Gruta, Nicole L ^a   Gras, Stephanie ^a   Daley, Stephen R ^a   Thomas, Paul G ^b   Rossjohn, Jamie ^a,c  

^a MONASH UNIVERSITY   (Australia)

^b ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^c CARDIFF UNIVERSITY SCHOOL OF MEDICINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

MAJOR HISTOCOMPATIBILITY ANTIGEN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; T LYMPHOCYTE RECEPTOR; HLA ANTIGEN CLASS 1; HLA ANTIGEN CLASS 2; LYMPHOCYTE ANTIGEN RECEPTOR;

ANTIGEN RECOGNITION; HUMAN; LYMPHOCYTE FUNCTION; MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; ANIMAL; ANTIBODY SPECIFICITY; BIOLOGICAL MODEL; CHEMISTRY; GENETICS; HISTORY; IMMUNOGENETICS; IMMUNOLOGY; MAJOR HISTOCOMPATIBILITY COMPLEX; MOLECULAR EVOLUTION; MOLECULAR MODEL; SYSTEMS BIOLOGY;

ANIMALS; ANTIBODY DIVERSITY; EVOLUTION, MOLECULAR; HISTOCOMPATIBILITY ANTIGENS CLASS I; HISTOCOMPATIBILITY ANTIGENS CLASS II; HISTORY, 20TH CENTURY; HISTORY, 21ST CENTURY; HUMANS; IMMUNOGENETICS; MAJOR HISTOCOMPATIBILITY COMPLEX; MODELS, GENETIC; MODELS, IMMUNOLOGICAL; MODELS, MOLECULAR; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; SYSTEMS BIOLOGY; T-LYMPHOCYTES;

EID: 85045149878     PISSN: 14741733     EISSN: 14741741     Source Type: Journal    
DOI: 10.1038/s41577-018-0007-5     Document Type: Review

References (134)

1. Zinkernagel, R. M. & Doherty, P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248, 701-702 (1974).
2. Hedrick, S. M., Cohen, D. I., Nielsen, E. A. & Davis, M. M. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature 308, 149-153 (1984).
3. Yanagi, Y. et al. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature 308, 145-149 (1984).
4. Rossjohn, J. et al. T cell antigen receptor recognition of antigen-presenting molecules. Annu. Rev. Immunol. 33, 169-200 (2015).
5. Rudolph, M. G., Stanfield, R. L. & Wilson, I. A. How TCRs bind MHCs, peptides, and coreceptors. Annu. Rev. Immunol. 24, 419-466 (2006).
6. van der Merwe, P. A. & Dushek, O. Mechanisms for T cell receptor triggering. Nat. Rev. Immunol. 11, 47-55 (2011).
7. Feng, D., Bond, C. J., Ely, L. K., Maynard, J. & Garcia, K. C. Structural evidence for a germlineencoded T cell receptor-major histocompatibility complex interaction 'codon'. Nat. Immunol. 8, 975-983 (2007).
8. Garcia, K. C., Adams, J. J., Feng, D. & Ely, L. K. The molecular basis of TCR germline bias for MHC is surprisingly simple. Nat. Immunol. 10, 143-147 (2009).
9. Marrack, P., Scott-Browne, J. P., Dai, S., Gapin, L. & Kappler, J. W. Evolutionarily conserved amino acids that control TCR-MHC interaction. Annu. Rev. Immunol. 26, 171-203 (2008).
10. Scott-Browne, J. P., White, J., Kappler, J. W., Gapin, L. & Marrack, P. Germline-encoded amino acids in the alphabeta T-cell receptor control thymic selection. Nature 458, 1043-1046 (2009).
11. Yin, L., Scott-Browne, J., Kappler, J. W., Gapin, L. & Marrack, P. T cells and their eons-old obsession with MHC. Immunol. Rev. 250, 49-60 (2012).
12. Jerne, N. K. The somatic generation of immune recognition. Eur. J. Immunol. 1, 1-9 (1971).
13. Rangarajan, S. & Mariuzza, R. A. T cell receptor bias for MHC: co-evolution or co-receptors? Cell. Mol. Life Sci. 71, 3059-3068 (2014).
14. Tikhonova, A. N. et al. alphabeta T cell receptors that do not undergo major histocompatibility complexspecific thymic selection possess antibody-like recognition specificities. Immunity 36, 79-91 (2012).
15. Van Laethem, F. et al. Deletion of CD4 and CD8 coreceptors permits generation of alphabetaT cells that recognize antigens independently of the MHC. Immunity 27, 735-750 (2007).
16. Van Laethem, F. et al. Lck availability during thymic selection determines the recognition specificity of the T cell repertoire. Cell 154, 1326-1341 (2013).
17. Van Laethem, F., Tikhonova, A. N. & Singer, A. MHC restriction is imposed on a diverse T cell receptor repertoire by CD4 and CD8 co-receptors during thymic selection. Trends Immunol. 33, 437-441 (2012).
18. Yewdell, J. W. & Haeryfar, S. M. Understanding presentation of viral antigens to CD8+ T cells in vivo: the key to rational vaccine design. Annu. Rev. Immunol. 23, 651-682 (2005).
19. Petersen, J., Purcell, A. & Rossjohn, J. Post-translationally modified T cell epitopes: immune recognition and immunotherapy. J. Mol. Med. 87, 1045-1051 (2009).
20. Godfrey, D. I., Uldrich, A. P., McCluskey, J., Rossjohn, J. & Moody, D. B. The burgeoning family of unconventional T cells. Nat. Immunol. 16, 1114-1123 (2015).
21. Van Rhijn, I., Godfrey, D. I., Rossjohn, J. & Moody, D. B. Lipid and small-molecule display by CD1 and MR1. Nat. Rev. Immunol. 15, 643-654 (2015).
22. Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L. & Godfrey, D. I. Recognition of CD1d-restricted antigens by natural killer T cells. Nat. Rev. Immunol. 12, 845-857 (2012).
23. Bjorkman, P. J. et al. Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329, 506-512 (1987).
24. Burrows, S. R., Rossjohn, J. & McCluskey, J. Have we cut ourselves too short in mapping CTL epitopes? Trends Immunol. 27, 11-16 (2006).
25. Brown, J. et al. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364, 33-39 (1993).
26. Adams, E. J. & Luoma, A. M. The adaptable major histocompatibility complex (MHC) fold: structure and function of nonclassical and MHC class I-like molecules. Annu. Rev. Immunol. 31, 529-561 (2013).
27. Henderson, K. N. et al. A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease. Immunity 27, 23-34 (2007).
28. Smith, K. J. et al. An altered position of the alpha 2 helix of MHC class I is revealed by the crystal structure of HLA-B3501. Immunity 4, 203-213 (1996).
29. Tynan, F. E. et al. High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I. Implications for T-cell receptor engagement and T-cell immunodominance. J. Biol. Chem. 280, 23900-23909 (2005).
30. Turner, S. J., Doherty, P. C., McCluskey, J. & Rossjohn, J. Structural determinants of T-cell receptor bias in immunity. Nat. Rev. Immunol. 6, 883-894 (2006).
31. Lefranc, M. P. IMGT, the international ImMunoGeneTics database. Nucleic Acids Res. 29, 207-209 (2001).
32. Davis, M. M. & Bjorkman, P. J. T-cell antigen receptor genes and T-cell recognition. Nature 334, 395-402 (1988).
33. McDonald, B. D., Bunker, J. J., Erickson, S. A., Oh-Hora, M. & Bendelac, A. Crossreactive alphabeta T cell receptors are the predominant targets of thymocyte negative selection. Immunity 43, 859-869 (2015).
34. Merkenschlager, M. et al. How many thymocytes audition for selection? J. Exp. Med. 186, 1149-1158 (1997).
35. Sinclair, C., Bains, I., Yates, A. J. & Seddon, B. Asymmetric thymocyte death underlies the CD4:CD8 T-cell ratio in the adaptive immune system. Proc. Natl Acad. Sci. USA 110, E2905-E2914 (2013).
36. Zerrahn, J., Held, W. & Raulet, D. H. The MHC reactivity of the T cell repertoire prior to positive and negative selection. Cell 88, 627-636 (1997).
37. Huseby, E. S. et al. How the T cell repertoire becomes peptide and MHC specific. Cell 122, 247-260 (2005).
38. Ignatowicz, L., Kappler, J. & Marrack, P. The repertoire of T cells shaped by a single MHC/peptide ligand. Cell 84, 521-529 (1996).
39. Chu, H. H., Moon, J. J., Kruse, A. C., Pepper, M. & Jenkins, M. K. Negative selection and peptide chemistry determine the size of naive foreign peptide-MHC class II-specific CD4+ T cell populations. J. Immunol. 185, 4705-4713 (2010).
40. Huseby, E. S., Crawford, F., White, J., Kappler, J. & Marrack, P. Negative selection imparts peptide specificity to the mature T cell repertoire. Proc. Natl Acad. Sci. USA 100, 11565-11570 (2003).
41. Turner, J. M. et al. Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. Cell 60, 755-765 (1990).
42. Veillette, A., Bookman, M. A., Horak, E. M. & Bolen, J. B. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosineprotein kinase p56lck. Cell 55, 301-308 (1988).
43. Artyomov, M. N., Lis, M., Devadas, S., Davis, M. M. & Chakraborty, A. K. CD4 and CD8 binding to MHC molecules primarily acts to enhance Lck delivery. Proc. Natl Acad. Sci. USA 107, 16916-16921 (2010).
44. Li, Q. J. et al. CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse. Nat. Immunol. 5, 791-799 (2004).
45. Stepanek, O. et al. Coreceptor scanning by the T cell receptor provides a mechanism for T cell tolerance. Cell 159, 333-345 (2014).
46. Scott-Browne, J. P. et al. Evolutionarily conserved features contribute to ab t cell receptor specificity. Immunity 35, 526-535 (2011).
47. Holland, S. J. et al. The T-cell receptor is not hardwired to engage MHC ligands. Proc. Natl Acad. Sci. USA 109, E3111-E3118 (2012).
48. Silberman, D. et al. Class II major histocompatibility complex mutant mice to study the germ-line bias of T-cell antigen receptors. Proc. Natl Acad. Sci. USA 113, E5608-E5617 (2016).
49. Garboczi, D. N. et al. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature 384, 134-141 (1996).
50. Garcia, K. C. et al. An alphabeta T cell receptor structure at 2. 5A and its orientation in the TCR-MHC complex. Science 274, 209-219 (1996).
51. Garcia, K. C. et al. Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science 279, 1166-1172 (1998).
52. Ding, Y. H. et al. Two human T cell receptors bind in a similar diagonal mode to the HLA-A2/Tax peptide complex using different TCR amino acids. Immunity 8, 403-411 (1998).
53. Manning, T. C. et al. Alanine scanning mutagenesis of an alphabeta T cell receptor: mapping the energy of antigen recognition. Immunity 8, 413-425 (1998).
54. Reinherz, E. L. et al. The crystal structure of a T cell receptor in complex with peptide and MHC class II. Science 286, 1913-1921 (1999).
55. Reiser, J. B. et al. A T cell receptor CDR3beta loop undergoes conformational changes of unprecedented magnitude upon binding to a peptide/MHC class I complex. Immunity 16, 345-354 (2002).
56. Reiser, J. B. et al. CDR3 loop flexibility contributes to the degeneracy of TCR recognition. Nat. Immunol. 4, 241-247 (2003).
57. Kjer-Nielsen, L. et al. A structural basis for the selection of dominant alphabeta T cell receptors in antiviral immunity. Immunity 18, 53-64 (2003).
58. Stewart-Jones, G. B., McMichael, A. J., Bell, J. I., Stuart, D. I. & Jones, E. Y. A structural basis for immunodominant human T cell receptor recognition. Nat. Immunol. 4, 657-663 (2003).
59. Archbold, J. K. et al. Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition. J. Exp. Med. 206, 209-219 (2009).
60. Deng, L. et al. Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor. Nat. Immunol. 8, 398-408 (2007).
61. Chen, J. L. et al. Structural and kinetic basis for heightened immunogenicity of T cell vaccines. J. Exp. Med. 201, 1243-1255 (2005).
62. Colf, L. A. et al. How a single T cell receptor recognizes both self and foreign MHC. Cell 129, 135-146 (2007).
63. Macdonald, W. A. et al. T cell allorecognition via molecular mimicry. Immunity 31, 897-908 (2009).
64. Hahn, M., Nicholson, M. J., Pyrdol, J. & Wucherpfennig, K. W. Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor. Nat. Immunol. 6, 490-496 (2005).
65. Li, Y. et al. Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule. EMBO J. 24, 2968-2979 (2005).
66. Borbulevych, O. Y. et al. T cell receptor cross-reactivity directed by antigen-dependent tuning of peptide-MHC molecular flexibility. Immunity 31, 885-896 (2009).
67. Tynan, F. E. et al. A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule. Nat. Immunol. 8, 268-276 (2007).
68. Tynan, F. E. et al. T cell receptor recognition of a 'superbulged' major histocompatibility complex class I-bound peptide. Nat. Immunol. 6, 1114-1122 (2005).
69. Burrows, S. R. et al. Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability. Proc. Natl Acad. Sci. USA 107, 10608-10613 (2010).
70. Turner, S. J. et al. Lack of prominent peptide-major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T cell populations. Nat. Immunol. 6, 382-389 (2005).
71. Day, E. B. et al. Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8+ T-cell responses. Proc. Natl Acad. Sci. USA 108, 9536-9541 (2011).
72. Gras, S., Kjer-Nielsen, L., Burrows, S. R., McCluskey, J. & Rossjohn, J. T-cell receptor bias and immunity. Curr. Opin. Immunol. 20, 119-125 (2008).
73. Borg, N. A. et al. The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition. Nat. Immunol. 6, 171-180 (2005).
74. Gras, S. et al. The shaping of T cell receptor recognition by self-tolerance. Immunity 30, 193-203 (2009).
75. Dai, S. et al. Crossreactive T cells spotlight the germline rules for [alpha][beta] T cell-receptor interactions with MHC molecules. Immunity 28, 324-334 (2008).
76. Blevins, S. J. et al. How structural adaptability exists alongside HLA-A2 bias in the human alphabeta TCR repertoire. Proc. Natl Acad. Sci. USA 113, E1276-E1285 (2016).
77. Berman, H. M. et al. The protein data bank. Nucleic Acids Res. 28, 235-242 (2000).
78. Ladell, K. et al. A molecular basis for the control of preimmune escape variants by HIV-specific CD8+ T cells. Immunity 38, 425-436 (2013).
79. Petersen, J. et al. Determinants of gliadin-specific T cell selection in celiac disease. J. Immunol. 194, 6112-6122 (2015).
80. Broughton, S. E. et al. Biased T cell receptor usage directed against human leukocyte antigen DQ8-restricted gliadin peptides is associated with celiac disease. Immunity 37, 611-621 (2012).
81. Petersen, J. et al. T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac disease. Nat. Struct. Mol. Biol. 21, 480-488 (2014).
82. Gras, S. et al. A structural basis for varied TCR usage against an immunodominant EBV antigen restricted to a HLA-B8 molecule. J. Immunol. 188, 311-321 (2012).
83. Gras, S. et al. Allelic polymorphism in the T cell receptor and its impact on immune responses. J. Exp. Med. 207, 1555-1567 (2010).
84. Sethi, D. K. et al. A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC. J. Exp. Med. 208, 91-102 (2011).
85. Sethi, D. K., Gordo, S., Schubert, D. A. & Wucherpfennig, K. W. Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop. Nat. Commun. 4, 2623 (2013).
86. Yin, L. et al. A single T cell receptor bound to major histocompatibility complex class I and class II glycoproteins reveals switchable TCR conformers. Immunity 35, 23-33 (2011).
87. Bulek, A. M. et al. Structural basis for the killing of human beta cells by CD8+ T cells in type 1 diabetes. Nat. Immunol. 13, 283-289 (2012).
88. Stewart-Jones, G. B. et al. Structural features underlying T-cell receptor sensitivity to concealed MHC class I micropolymorphisms. Proc. Natl Acad. Sci. USA 109, E3483-E3492 (2012).
89. Liu, Y. C. et al. A molecular basis for the interplay between T cells, viral mutants, and human leukocyte antigen micropolymorphism. J. Biol. Chem. 289, 16688-16698 (2014).
90. Birnbaum, M. E. et al. Deconstructing the peptide-MHC specificity of T cell recognition. Cell 157, 1073-1087 (2014).
91. Cole, D. K. et al. Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity. J. Clin. Invest. 126, 3626-3626 (2016).
92. Adams, J. J. et al. Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity. Nat. Immunol. 17, 87-94 (2015).
93. Adams, J. J. et al. T cell receptor signaling is limited by docking geometry to peptide-major histocompatibility complex. Immunity 35, 681-693 (2011).
94. Stadinski, B. D. et al. A role for differential variable gene pairing in creating T cell receptors specific for unique major histocompatibility ligands. Immunity 35, 694-704 (2011).
95. Culshaw, A. et al. Germline bias dictates crossserotype reactivity in a common dengue-virus-specific CD8+ T cell response. Nat. Immunol. 18, 1228-1237 (2017).
96. Van Braeckel-Budimir, N. et al. A T cell receptor locus harbors a malaria-specific immune response gene. Immunity 47, 835-847 (2017).
97. Beringer, D. X. et al. T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex. Nat. Immunol. 16, 1153-1161 (2015).
98. Gras, S. et al. Reversed T cell receptor docking on a major histocompatibility class I complex limits involvement in the immune response. Immunity 45, 749-760 (2016).
99. Garcia, K. C. Reconciling views on T cell receptor germline bias for MHC. Trends Immunol. 33, 429-436 (2012).
100. Parrish, H. L., Deshpande, N. R., Vasic, J. & Kuhns, M. S. Functional evidence for TCR-intrinsic specificity for MHCII. Proc. Natl Acad. Sci. USA 113, 3000-3005 (2016).
101. Yin, Y., Wang, X. X. & Mariuzza, R. A. Crystal structure of a complete ternary complex of T-cell receptor, peptide-MHC, and CD4. Proc. Natl Acad. Sci. USA 109, 5405-5410 (2012).
102. He, Y. et al. Identification of the docking site for CD3 on the T cell receptor beta chain by solution NMR. J. Biol. Chem. 290, 19796-19805 (2015).
103. Li, Y., Yin, Y. & Mariuzza, R. A. Structural and biophysical insights into the role of CD4 and CD8 in T cell activation. Front. Immunol. 4, 206 (2013).
104. Barnd, D. L., Lan, M. S., Metzgar, R. S. & Finn, O. J. Specific, major histocompatibility complexunrestricted recognition of tumor-associated mucins by human cytotoxic T cells. Proc. Natl Acad. Sci. USA 86, 7159-7163 (1989).
105. Hanada, K., Wang, Q. J., Inozume, T. & Yang, J. C. Molecular identification of an MHC-independent ligand recognized by a human alpha/beta T-cell receptor. Blood 117, 4816-4825 (2011).
106. Magarian-Blander, J., Ciborowski, P., Hsia, S., Watkins, S. C. & Finn, O. J. Intercellular and intracellular events following the MHC-unrestricted TCR recognition of a tumor-specific peptide epitope on the epithelial antigen MUC1. J. Immunol. 160, 3111-3120 (1998).
107. Rao, A., Ko, W. W., Faas, S. J. & Cantor, H. Binding of antigen in the absence of histocompatibility proteins by arsonate-reactive T-cell clones. Cell 36, 879-888 (1984).
108. Siliciano, R. F. et al. Direct evidence for the existence of nominal antigen binding sites on T cell surface Ti alpha-beta heterodimers of MHC-restricted T cell clones. Cell 47, 161-171 (1986).
109. Ferreira, M. A. et al. Quantitative trait loci for CD4:CD8 lymphocyte ratio are associated with risk of type 1 diabetes and HIV-1 immune control. Am. J. Hum. Genet. 86, 88-92 (2010).
110. Gulwani-Akolkar, B. et al. Do HLA genes play a prominent role in determining T cell receptor V alpha segment usage in humans? J. Immunol. 154, 3843-3851 (1995).
111. Klarenbeek, P. L. et al. Somatic variation of T-cell receptor genes strongly associate with HLA class restriction. PLOS One 10, e0140815 (2015).
112. Sim, B. C., Zerva, L., Greene, M. I. & Gascoigne, N. R. Control of MHC restriction by TCR Valpha CDR1 and CDR2. Science 273, 963-966 (1996).
113. Rubelt, F. et al. Individual heritable differences result in unique cell lymphocyte receptor repertoires of naive and antigen-experienced cells. Nat. Commun. 7, 11112 (2016).
114. Zvyagin, I. V. et al. Distinctive properties of identical twins' TCR repertoires revealed by high-throughput sequencing. Proc. Natl Acad. Sci. USA 111, 5980-5985 (2014).
115. Emerson, R. O. et al. Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire. Nat. Genet. 49, 659-665 (2017).
116. Sharon, E. et al. Genetic variation in MHC proteins is associated with T cell receptor expression biases. Nat. Genet. 48, 995-1002 (2016).
117. Madi, A. et al. T cell receptor repertoires of mice and humans are clustered in similarity networks around conserved public CDR3 sequences. Elife 6, e22057 (2017).
118. Dash, P. et al. Quantifiable predictive features define epitope-specific T cell receptor repertoires. Nature 547, 89-93 (2017).
119. Glanville, J. et al. Identifying specificity groups in the T cell receptor repertoire. Nature 547, 94-98 (2017).
120. Mayr, E. Cause and effect in biology. Science 134, 1501-1506 (1961).
121. Altman, J. D. et al. Phenotypic analysis of antigenspecific T lymphocytes. Science 274, 94-96 (1996).
122. Ding, Y. H., Baker, B. M., Garboczi, D. N., Biddison, W. E. & Wiley, D. C. Four A6-TCR/peptide/ HLA-A2 structures that generate very different T cell signals are nearly identical. Immunity 11, 45-56 (1999).
123. Reiser, J. B. et al. Crystal structure of a T cell receptor bound to an allogeneic MHC molecule. Nat. Immunol. 1, 291-297 (2000).
124. Degano, M. et al. A functional hot spot for antigen recognition in a superagonist TCR/MHC complex. Immunity 12, 251-261 (2000).
125. Moon, J. J. et al. Naive CD4+ T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity 27, 203-213 (2007).
126. Robins, H. S. et al. Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood 114, 4099-4107 (2009).
127. Dash, P. et al. Paired analysis of TCRalpha and TCRbeta chains at the single-cell level in mice. J. Clin. Invest. 121, 288-295 (2011).
128. Wang, G. C., Dash, P., McCullers, J. A., Doherty, P. C. & Thomas, P. G. T cell receptor alphabeta diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection. Sci. Transl. Med. 4, 128ra142 (2012).
129. Kim, S. M. et al. Analysis of the paired TCR alpha-and beta-chains of single human T cells. PLOS ONE 7, e37338 (2012).
130. Bolotin, D. A. et al. Next generation sequencing for TCR repertoire profiling: platform-specific features and correction algorithms. Eur. J. Immunol. 42, 3073-3083 (2012).
131. Bolotin, D. A. et al. MiTCR: software for T-cell receptor sequencing data analysis. Nat. Methods 10, 813-814 (2013).
132. Turchaninova, M. A. et al. Pairing of T-cell receptor chains via emulsion PCR. Eur. J. Immunol. 43, 2507-2515 (2013).
133. Howie, B. et al. High-throughput pairing of T cell receptor alpha and beta sequences. Sci. Transl. Med. 7, 301ra131 (2015).
134. Stubbington, M. J. T. et al. T cell fate and clonality inference from single-cell transcriptomes. Nat. Methods 13, 329-332 (2016).