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. 2013 Jan 11;4(1):8–16. doi: 10.1007/s13238-012-2077-7

Recognition of self and altered self by T cells in autoimmunity and allergy

Lei Yin 1,✉, Shaodong Dai 2, Gina Clayton 1, Wei Gao 2, Yang Wang 2, John Kappler 1,3, Philippa Marrack 1,4,✉
PMCID: PMC3951410  NIHMSID: NIHMS559023  PMID: 23307779

Abstract

T cell recognition of foreign peptide antigen and tolerance to self peptides is key to the proper function of the immune system. Usually, in the thymus T cells that recognize self MHC + self peptides are deleted and those with the potential to recognize self MHC + foreign peptides are selected to mature. However there are exceptions to these rules. Autoimmunity and allergy are two of the most common immune diseases that can be related to recognition of self. Many genes work together to lead to autoimmunity. Of those, particular MHC alleles are the most strongly associated, reflecting the key importance of MHC presentation of self peptides in autoimmunity. T cells specific for combinations of self MHC and self peptides may escape thymus deletion, and thus be able to drive autoimmunity, for several reasons: the relevant self peptide may be presented at low abundance in the thymus but at high level in particular peripheral tissues; the relevant self peptide may bind to MHC in an unusual register, not present in the thymus but apparent elsewhere; finally the relevant self peptide may be post translationally modified in a tissue specific fashion. In some types of allergy, the peptide + MHC combination may also be fully derived from self. However the combination in question may be modified by the presence of other ligands, such as small drug molecules or metal ions. Thus these types of allergies may act like the post translationally modified peptides involved some types of autoimmunity.

Keywords: altered self, neoantigen, antigen presenting, T cell recognition, autoimmunity, allergy, diabetes, dermatitis, drug hypersensitivity

Contributor Information

Lei Yin, Email: yinl@njhealth.org.

Philippa Marrack, Email: marrackp@njhealth.org.

References

  1. Ada G.L., Rose N.R. The initiation and early development of autoimmune diseases. Clin Immunol Immunopathol. 1988;47:3–9. doi: 10.1016/0090-1229(88)90139-0. [DOI] [PubMed] [Google Scholar]
  2. Adams J.J., Narayanan S., Liu B., Birnbaum M.E., Kruse A.C., Bowerman N.A., Chen W., Levin A.M., Connolly J.M., Zhu C., et al. T cell receptor signaling is limited by docking geometry to peptide-major histocompatibility complex. Immunity. 2011;35:681–693. doi: 10.1016/j.immuni.2011.09.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alarcon B., Mestre D., Martinez-Martin N. The immunological synapse: a cause or consequence of T-cell receptor triggering? Immunology. 2011;133:420–425. doi: 10.1111/j.1365-2567.2011.03458.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Allanore Y., Saad M., Dieude P., Avouac J., Distler J.H., Amouyel P., Matucci-Cerinic M., Riemekasten G., Airo P., Melchers I., et al. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis. PLoS Genet. 2011;7:e1002091. doi: 10.1371/journal.pgen.1002091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Anderson M.S., Venanzi E.S., Klein L., Chen Z., Berzins S.P., Turley S.J., von Boehmer H., Bronson R., Dierich A., Benoist C., et al. Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002;298:1395–1401. doi: 10.1126/science.1075958. [DOI] [PubMed] [Google Scholar]
  6. Banchereau J., Steinman R.M. Dendritic cells and the control of immunity. Nature. 1998;392:245–252. doi: 10.1038/32588. [DOI] [PubMed] [Google Scholar]
  7. Bevan M.J., Hunig T. T cells respond preferentially to antigens that are similar to self H-2. Proc Natl Acad Sci U S A. 1981;78:1843–1847. doi: 10.1073/pnas.78.3.1843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bluestone J.A. New perspectives of CD28-B7-mediated T cell costimulation. Immunity. 1995;2:555–559. doi: 10.1016/1074-7613(95)90000-4. [DOI] [PubMed] [Google Scholar]
  9. Bluthmann H., Kisielow P., Uematsu Y., Malissen M., Krimpenfort P., Berns A., von Boehmer H., Steinmetz M. T-cell-specific deletion of T-cell receptor transgenes allows functional rearrangement of endogenous alpha- and beta-genes. Nature. 1988;334:156–159. doi: 10.1038/334156a0. [DOI] [PubMed] [Google Scholar]
  10. Bogdanos D.P., Smyk D.S., Rigopoulou E.I., Mytilinaiou M.G., Heneghan M.A., Selmi C., Gershwin M.E. Twin studies in autoimmune disease: genetics, gender and environment. J Autoimmun. 2011;38:J156–169. doi: 10.1016/j.jaut.2011.11.003. [DOI] [PubMed] [Google Scholar]
  11. Brand O.J., Gough S.C. Immunogenetic mechanisms leading to thyroid autoimmunity: recent advances in identifying susceptibility genes and regions. Curr Genomics. 2012;12:526–541. doi: 10.2174/138920211798120790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Browne S.K., Holland S.M. Immunodeficiency secondary to anticytokine autoantibodies. Curr Opin Allergy Clin Immunol. 2010;10:534–541. doi: 10.1097/ACI.0b013e3283402b41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Burrows S.R., Chen Z., Archbold J.K., Tynan F.E., Beddoe T., Kjer-Nielsen L., Miles J.J., Khanna R., Moss D.J., Liu Y.C., et al. Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability. Proc Natl Acad Sci U S A. 2010;107:10608–10613. doi: 10.1073/pnas.1004926107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Callahan M.K., Wolchok J.D., Allison J.P. Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy. Semin Oncol. 2010;37:473–484. doi: 10.1053/j.seminoncol.2010.09.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Colf L.A., Bankovich A.J., Hanick N.A., Bowerman N.A., Jones L.L., Kranz D.M., Garcia K.C. How a single T cell receptor recognizes both self and foreign MHC. Cell. 2007;129:135–146. doi: 10.1016/j.cell.2007.01.048. [DOI] [PubMed] [Google Scholar]
  16. Croft M. The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol. 2009;9:271–285. doi: 10.1038/nri2526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dai S., Huseby E.S., Rubtsova K., Scott-Browne J., Crawford F., Macdonald W.A., Marrack P., Kappler J.W. Crossreactive T Cells spotlight the germline rules for alphabeta T cell-receptor interactions with MHC molecules. Immunity. 2008;28:324–334. doi: 10.1016/j.immuni.2008.01.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Day E.B., Guillonneau C., Gras S., La Gruta N.L., Vignali D.A., Doherty P.C., Purcell A.W., Rossjohn J., Turner S.J. Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8+ T-cell responses. Proc Natl Acad Sci U S A. 2011;108:9536–9541. doi: 10.1073/pnas.1106851108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Depaz R., Granger B., Cournu-Rebeix I., Bouafia A., Fontaine B. Genetics for understanding and predicting clinical progression in multiple sclerosis. Rev Neurol (Paris) 2011;167:791–801. doi: 10.1016/j.neurol.2011.02.043. [DOI] [PubMed] [Google Scholar]
  20. Deshmukh H.A., Maiti A.K., Kim-Howard X.R., Rojas-Villarraga A., Guthridge J.M., Anaya J.M., Nath S.K. Evaluation of 19 autoimmune disease-associated loci with rheumatoid arthritis in a Colombian population: evidence for replication and gene-gene interaction. J Rheumatol. 2011;38:1866–1870. doi: 10.3899/jrheum.110199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Dhein J., Walczak H., Baumler C., Debatin K.M., Krammer P.H. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95) Nature. 1995;373:438–441. doi: 10.1038/373438a0. [DOI] [PubMed] [Google Scholar]
  22. Dinarello C.A. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol. 2002;20:S1–13. [PubMed] [Google Scholar]
  23. Dolfi D.V., Katsikis P.D. CD28 and CD27 costimulation of CD8+ T cells: a story of survival. Adv Exp Med Biol. 2007;590:149–170. doi: 10.1007/978-0-387-34814-8_11. [DOI] [PubMed] [Google Scholar]
  24. Evnouchidou I., Birtley J., Seregin S., Papakyriakou A., Zervoudi E., Samiotaki M., Panayotou G., Giastas P., Petrakis O., Georgiadis D., et al. A common single nucleotide polymorphism in endoplasmic reticulum aminopeptidase 2 induces a specificity switch that leads to altered antigen processing. J Immunol. 2012;189:2383–2392. doi: 10.4049/jimmunol.1200918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Feng D., Bond C.J., Ely L.K., Maynard J., Garcia K.C. Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction ‘codon'. Nat Immunol. 2007;8:975–983. doi: 10.1038/ni1502. [DOI] [PubMed] [Google Scholar]
  26. Fierabracci, A., Milillo, A., Locatelli, F., and Fruci, D. (2012). The putative role of endoplasmic reticulum aminopeptidases in autoimmunity: Insights from genomic-wide association studies. Autoimmun Rev. (In Press). [DOI] [PubMed]
  27. Gambineri E., Torgerson T.R., Ochs H.D. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol. 2003;15:430–435. doi: 10.1097/00002281-200307000-00010. [DOI] [PubMed] [Google Scholar]
  28. 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. 2009;10:143–147. doi: 10.1038/ni.f.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Garcia K.C., Degano M., Pease L.R., Huang M., Peterson P.A., Teyton L., Wilson I.A. Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science. 1998;279:1166–1172. doi: 10.1126/science.279.5354.1166. [DOI] [PubMed] [Google Scholar]
  30. Garcia K.C., Degano M., Stanfield R.L., Brunmark A., Jackson M.R., Peterson P.A., Teyton L., Wilson I.A. An alphabeta T cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex. Science. 1996;274:209–219. doi: 10.1126/science.274.5285.209. [DOI] [PubMed] [Google Scholar]
  31. Garcia K.C., Teyton L., Wilson I.A. Structural basis of T cell recognition. Annu Rev Immunol. 1999;17:369–397. doi: 10.1146/annurev.immunol.17.1.369. [DOI] [PubMed] [Google Scholar]
  32. Grumet F.C., Coukell A., Bodmer J.G., Bodmer W.F., McDevitt H.O. Histocompatibility (HL-A) antigens associated with systemic lupus erythematosus. A possible genetic predisposition to disease. N Engl J Med. 1971;285:193–196. doi: 10.1056/NEJM197107222850403. [DOI] [PubMed] [Google Scholar]
  33. Guerini F.R., Cagliani R., Forni D., Agliardi C., Caputo D., Cassinotti A., Galimberti D., Fenoglio C., Biasin M., Asselta R., et al. A functional variant in ERAP1 predisposes to multiple sclerosis. PLoS One. 2012;7:e29931. doi: 10.1371/journal.pone.0029931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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. 2005;6:490–496. doi: 10.1038/ni1187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Haskins K., Cooke A. CD4 T cells and their antigens in the pathogenesis of autoimmune diabetes. Curr Opin Immunol. 2011;23:739–745. doi: 10.1016/j.coi.2011.08.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Heino M., Peterson P., Kudoh J., Shimizu N., Antonarakis S.E., Scott H.S., Krohn K. APECED mutations in the autoimmune regulator (AIRE) gene. Hum Mutat. 2001;18:205–211. doi: 10.1002/humu.1176. [DOI] [PubMed] [Google Scholar]
  37. Hintzen R.Q., de Jong R., Lens S.M., van Lier R.A. CD27: marker and mediator of T-cell activation? Immunol Today. 1994;15:307–311. doi: 10.1016/0167-5699(94)90077-9. [DOI] [PubMed] [Google Scholar]
  38. Illing P.T., Vivian J.P., Dudek N.L., Kostenko L., Chen Z., Bharadwaj M., Miles J.J., Kjer-Nielsen L., Gras S., Williamson N.A., et al. Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature. 2012;486:554–558. doi: 10.1038/nature11147. [DOI] [PubMed] [Google Scholar]
  39. Inaba K., Metlay J.P., Crowley M.T., Witmer-Pack M., Steinman R.M. Dendritic cells as antigen presenting cells in vivo. Int Rev Immunol. 1990;6:197–206. doi: 10.3109/08830189009056630. [DOI] [PubMed] [Google Scholar]
  40. Ireland J.M., Unanue E.R. Processing of proteins in autophagy vesicles of antigen-presenting cells generates citrullinated peptides recognized by the immune system. Autophagy. 2012;8:429–430. doi: 10.4161/auto.19261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Jarchum I., DiLorenzo T.P. Ins2 deficiency augments spontaneous HLA-A*0201-restricted T cell responses to insulin. J Immunol. 2009;184:658–665. doi: 10.4049/jimmunol.0903414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Jenkins M.K., Schwartz R.H. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med. 1987;165:302–319. doi: 10.1084/jem.165.2.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Kappler J.W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987;49:273–280. doi: 10.1016/0092-8674(87)90568-X. [DOI] [PubMed] [Google Scholar]
  44. Kato Z., Stern J.N., Nakamura H.K., Miyashita N., Kuwata K., Kondo N., Strominger J.L. The autoimmune TCR-Ob.2F3 can bind to MBP85-99/HLA-DR2 having an unconventional mode as in TCR-Ob.1A12. Mol Immunol. 2010;48:314–320. doi: 10.1016/j.molimm.2010.07.010. [DOI] [PubMed] [Google Scholar]
  45. Kuhn K.A., Cozine C.L., Tomooka B., Robinson W.H., Holers V.M. Complement receptor CR2/CR1 deficiency protects mice from collagen-induced arthritis and associates with reduced autoantibodies to type II collagen and citrullinated antigens. Mol Immunol. 2008;45:2808–2819. doi: 10.1016/j.molimm.2008.01.036. [DOI] [PubMed] [Google Scholar]
  46. Lafferty K.J., Cunningham A.J. A new analysis of allogeneic interactions. Aust J Exp Biol Med Sci. 1975;53:27–42. doi: 10.1038/icb.1975.3. [DOI] [PubMed] [Google Scholar]
  47. Levisetti M.G., Suri A., Petzold S.J., Unanue E.R. The insulin-specific T cells of nonobese diabetic mice recognize a weak MHC-binding segment in more than one form. J Immunol. 2007;178:6051–6057. doi: 10.4049/jimmunol.178.10.6051. [DOI] [PubMed] [Google Scholar]
  48. Li Y., Huang Y., Lue J., Quandt J.A., Martin R., Mariuzza R.A. 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. 2005;24:2968–2979. doi: 10.1038/sj.emboj.7600771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Marrack P., Kappler J.W. Do MHCII-presented neoantigens drive type 1 diabetes and other autoimmune diseases? Cold Spring Harb Perspect Med. 2012;2:a007765. doi: 10.1101/cshperspect.a007765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. 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. 2008;26:171–203. doi: 10.1146/annurev.immunol.26.021607.090421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Maynard J., Petersson K., Wilson D.H., Adams E.J., Blondelle S.E., Boulanger M.J., Wilson D.B., Garcia K.C. Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity. Immunity. 2005;22:81–92. doi: 10.1016/j.immuni.2004.11.015. [DOI] [PubMed] [Google Scholar]
  52. McDevitt H.O., Bodmer W.F. HL-A, immune-response genes, and disease. Lancet. 1974;1:1269–1275. doi: 10.1016/S0140-6736(74)90021-X. [DOI] [PubMed] [Google Scholar]
  53. Mohan J.F., Levisetti M.G., Calderon B., Herzog J.W., Petzold S.J., Unanue E.R. Unique autoreactive T cells recognize insulin peptides generated within the islets of Langerhans in autoimmune diabetes. Nat Immunol. 2010;11:350–354. doi: 10.1038/ni.1850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Nakayama M., Beilke J.N., Jasinski J.M., Kobayashi M., Miao D., Li M., Coulombe M.G., Liu E., Elliott J.F., Gill R.G., et al. Priming and effector dependence on insulin B:9-23 peptide in NOD islet autoimmunity. J Clin Invest. 2007;117:1835–1843. doi: 10.1172/JCI31368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Pardoll D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–264. doi: 10.1038/nrc3239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Rainbow D.B., Esposito L., Howlett S.K., Hunter K.M., Todd J.A., Peterson L.B., Wicker L.S. Commonality in the genetic control of Type 1 diabetes in humans and NOD mice: variants of genes in the IL-2 pathway are associated with autoimmune diabetes in both species. Biochem Soc Trans. 2008;36:312–315. doi: 10.1042/BST0360312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Ramsdell F. Foxp3 and natural regulatory T cells: key to a cell lineage? Immunity. 2003;19:165–168. doi: 10.1016/S1074-7613(03)00207-3. [DOI] [PubMed] [Google Scholar]
  58. Ramsey C., Winqvist O., Puhakka L., Halonen M., Moro A., Kampe O., Eskelin P., Pelto-Huikko M., Peltonen L. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum Mol Genet. 2002;11:397–409. doi: 10.1093/hmg/11.4.397. [DOI] [PubMed] [Google Scholar]
  59. Reiser J.B., Darnault C., Gregoire C., Mosser T., Mazza G., Kearney A., van der Merwe P.A., Fontecilla-Camps J.C., Housset D., Malissen B. CDR3 loop flexibility contributes to the degeneracy of TCR recognition. Nat Immunol. 2003;4:241–247. doi: 10.1038/ni891. [DOI] [PubMed] [Google Scholar]
  60. Rubin B., Sonderstrup G. Citrullination of self-proteins and autoimmunity. Scand J Immunol. 2004;60:112–120. doi: 10.1111/j.0300-9475.2004.01457.x. [DOI] [PubMed] [Google Scholar]
  61. Sethi D.K., Schubert D.A., Anders A.K., Heroux A., Bonsor D.A., Thomas C.P., Sundberg E.J., Pyrdol J., Wucherpfennig K.W. A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC. J Exp Med. 2011;208:91–102. doi: 10.1084/jem.20100725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Sharpe A.H. Mechanisms of costimulation. Immunol Rev. 2009;229:5–11. doi: 10.1111/j.1600-065X.2009.00784.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Sloan-Lancaster J., Allen P.M. Signalling events in the anergy induction of T helper 1 cells. Ciba Found Symp. 1995;195:189–196. doi: 10.1002/9780470514849.ch13. [DOI] [PubMed] [Google Scholar]
  64. Sneller M.C., Wang J., Dale J.K., Strober W., Middelton L.A., Choi Y., Fleisher T.A., Lim M.S., Jaffe E.S., Puck J.M., et al. Clincal, immunologic, and genetic features of an autoimmune lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis. Blood. 1997;89:1341–1348. [PubMed] [Google Scholar]
  65. Stadinski B.D., Delong T., Reisdorph N., Reisdorph R., Powell R.L., Armstrong M., Piganelli J.D., Barbour G., Bradley B., Crawford F., et al. Chromogranin A is an autoantigen in type 1 diabetes. Nat Immunol. 2010;11:225–231. doi: 10.1038/ni.1844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Stadinski B.D., Zhang L., Crawford F., Marrack P., Eisenbarth G.S., Kappler J.W. Diabetogenic T cells recognize insulin bound to IAg7 in an unexpected, weakly binding register. Proc Natl Acad Sci U S A. 2010;107:10978–10983. doi: 10.1073/pnas.1006545107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Steinman R.M., Inaba K. Stimulation of the primary mixed leukocyte reaction. Crit Rev Immunol. 1985;5:331–348. [PubMed] [Google Scholar]
  68. Steinman R.M., Koide S., Witmer M., Crowley M., Bhardwaj N., Freudenthal P., Young J., Inaba K. The sensitization phase of T-cell-mediated immunity. Ann N Y Acad Sci. 1988;546:80–90. doi: 10.1111/j.1749-6632.1988.tb21622.x. [DOI] [PubMed] [Google Scholar]
  69. Suri A., Levisetti M.G., Unanue E.R. Do the peptide-binding properties of diabetogenic class II molecules explain autoreactivity? Curr Opin Immunol. 2008;20:105–110. doi: 10.1016/j.coi.2007.10.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Tynan F.E., Burrows S.R., Buckle A.M., Clements C.S., Borg N.A., Miles J.J., Beddoe T., Whisstock J.C., Wilce M.C., Silins S.L., et al. T cell receptor recognition of a 'super-bulged’ major histocompatibility complex class I-bound peptide. Nat Immunol. 2005;6:1114–1122. doi: 10.1038/ni1257. [DOI] [PubMed] [Google Scholar]
  71. Tynan F.E., Reid H.H., Kjer-Nielsen L., Miles J.J., Wilce M.C., Kostenko L., Borg N.A., Williamson N.A., Beddoe T., Purcell A.W., et al. A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule. Nat Immunol. 2007;8:268–276. doi: 10.1038/ni1432. [DOI] [PubMed] [Google Scholar]
  72. van Boekel M.A., Vossenaar E.R., van den Hoogen F.H., van Venrooij W.J. Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res. 2002;4:87–93. doi: 10.1186/ar395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. von Boehmer H., Teh H.S., Kisielow P. The thymus selects the useful, neglects the useless and destroys the harmful. Immunol Today. 1989;10:57–61. doi: 10.1016/0167-5699(89)90307-1. [DOI] [PubMed] [Google Scholar]
  74. Watts T.H. Staying alive: T cell costimulation, CD28, and Bcl-xL. J Immunol. 2010;185:3785–3787. doi: 10.4049/jimmunol.1090085. [DOI] [PubMed] [Google Scholar]
  75. Wherry E.J., Ha S.J., Kaech S.M., Haining W.N., Sarkar S., Kalia V., Subramaniam S., Blattman J.N., Barber D.L., Ahmed R. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity. 2007;27:670–684. doi: 10.1016/j.immuni.2007.09.006. [DOI] [PubMed] [Google Scholar]
  76. Wildin R.S., Smyk-Pearson S., Filipovich A.H. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet. 2002;39:537–545. doi: 10.1136/jmg.39.8.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Yin L., Crawford F., Marrack P., Kappler J.W., Dai S. T-cell receptor (TCR) interaction with peptides that mimic nickel offers insight into nickel contact allergy. Proc Natl Acad Sci U S A. 2012;109:18517–18522. doi: 10.1073/pnas.1215928109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Yin L., Huseby E., Scott-Browne J., Rubtsova K., Pinilla C., Crawford F., Marrack P., Dai S., Kappler J.W. A single T cell receptor bound to major histocompatibility complex class I and class II glycoproteins reveals switchable TCR conformers. Immunity. 2011;35:23–33. doi: 10.1016/j.immuni.2011.04.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Yin Y., Li Y., Kerzic M.C., Martin R., Mariuzza R.A. Structure of a TCR with high affinity for self-antigen reveals basis for escape from negative selection. EMBO J. 2011;30:1137–1148. doi: 10.1038/emboj.2011.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. 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 U S A. 2012;109:5405–5410. doi: 10.1073/pnas.1118801109. [DOI] [PMC free article] [PubMed] [Google Scholar]

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