Minor histocompatibility antigens: Presentation principles, recognition logic and the potential for a healing hand

Current Opinion in Organ Transplantation

Volumn 15, Issue 4, 2010, Pages 512-525

  Spencer, Charles T ^a   Gilchuk, Pavlo ^a   Dragovic, Srdjan M ^a   Joyce, Sebastian ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

antigen processing and presentation; minor histocompatibility antigen; peptide major histocompatibility complex T cell receptor recognition logic; topologic biochemistry; transplant immunity

Indexed keywords

ALLOANTIGEN; CALRETICULIN; CASPASE RECRUITMENT DOMAIN PROTEIN 15; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; GAMMA INTERFERON; HLA ANTIGEN CLASS 1; HLA DM ANTIGEN; HLA DR ANTIGEN; HLA DR2 ANTIGEN; HYDRALAZINE; INTERLEUKIN 12; INTERLEUKIN 18; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; ISONIAZID; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MINOR HISTOCOMPATIBILITY ANTIGEN; PROCAINAMIDE; T LYMPHOCYTE RECEPTOR; TOLL LIKE RECEPTOR; TRANSPORTER ASSOCIATED WITH ANTIGEN PROCESSING 1; TUMOR NECROSIS FACTOR ALPHA; XENOBIOTIC AGENT; LIGAND; LYMPHOCYTE ANTIGEN RECEPTOR;

ALLOGRAFT; ALLOTRANSPLANTATION; ANTIGEN DETECTION; ANTIGEN PRESENTATION; ANTIGEN RECOGNITION; AUTOPHAGY; BIOCHEMISTRY; BONE MARROW TRANSPLANTATION; CROSS PRESENTATION; DENDRITIC CELL; GRAFT REJECTION; GRAFT SURVIVAL; GRAFT VERSUS HOST REACTION; HISTOINCOMPATIBILITY; HLA TYPING; HUMAN; INFLAMMATION; MAJOR HISTOCOMPATIBILITY COMPLEX; MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION; NEUTROPHIL; NONHUMAN; REVIEW; SHORT TANDEM REPEAT; X RAY CRYSTALLOGRAPHY; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; GENETICS; GRAFT VS HOST DISEASE; IMMUNOLOGY; IMMUNOSUPPRESSIVE TREATMENT; PROCEDURES; PROTEIN CONFORMATION; STRUCTURE ACTIVITY RELATION; T LYMPHOCYTE; TRANSPLANTATION TOLERANCE;

ANIMALS; GRAFT REJECTION; GRAFT SURVIVAL; GRAFT VS HOST DISEASE; HUMANS; IMMUNOSUPPRESSION; INFLAMMATION; ISOANTIGENS; LIGANDS; MINOR HISTOCOMPATIBILITY ANTIGENS; MODELS, MOLECULAR; PROTEIN CONFORMATION; RECEPTORS, ANTIGEN, T-CELL; STRUCTURE-ACTIVITY RELATIONSHIP; T-LYMPHOCYTES; TRANSPLANTATION TOLERANCE; TRANSPLANTATION, HOMOLOGOUS;

EID: 77955230673     PISSN: 10872418     EISSN: 15317013     Source Type: Journal    
DOI: 10.1097/MOT.0b013e32833c1552     Document Type: Review

References (131)

1. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392:245-252.
2. Reise Sousa C. Activation of dendritic cells: translating innate into adaptive immunity. Curr Opin Immunol 2004; 16:21-25.
3. Trombetta ES, Mellman I. Cell biology of antigen processing in vitro and in vivo. Annu Rev Immunol 2005; 23:975-1028.
4. Cresswell P, Ackerman AL, Giodini A, et al. Mechanisms of MHC class Irestricted antigen processing and cross-presentation. Immunol Rev 2005; 207:145-157.
5. Wilson NS, Villadangos JA. Regulation of antigen presentation and crosspresentation in the dendritic cell network: facts, hypothesis, and immunological implications. Adv Immunol 2005; 86:241-305.
6. Chen Y, Demir Y, Valujskikh A, Heeger PS. The male minor transplantation antigen preferentially activates recipient CD4+ T cells through the indirect presentation pathway in vivo. J Immunol 2003; 171:6510-6518.
7. Thery C, Duban L, Segura E, et al. Indirect activation of naive CD4+ T cells by dendritic cell-derived exosomes. Nat Immunol 2002; 3:1156-1162.
8. Russmann H, Gerdemann U, Igwe EI, et al. Attenuated Yersinia pseudotuberculosis carrier vaccine for simultaneous antigen-specific CD4 and CD8 T-cell induction. Infect Immun 2003; 71:3463-3472.
9. Valentino MD, Hensley LL, Skrombolas D, et al. Identification of a dominant CD4 T cell epitope in the membrane lipoprotein Tul4 from Francisella tularensis LVS. Mol Immunol 2009; 46:1830-1838.
10. Matyszak MK, Young JL, Gaston JS. Uptake and processing of Chlamydia trachomatis by human dendritic cells. Eur J Immunol 2002; 32:742-751.
11. Dissanayake SK, Tuera N, Ostrand-Rosenberg S. Presentation of endogenously synthesized MHC class II-restricted epitopes by MHC class II cancer vaccines is independent of transporter associated with Ag processing and the proteasome. J Immunol 2005; 174:1811-1819.
12. Nimmerjahn F, Milosevic S, Behrends U, et al. Major histocompatibility complex class II-restricted presentation of a cytosolic antigen by autophagy. Eur J Immunol 2003; 33:1250-1259.
13. Paludan C, Schmid D, Landthaler M, et al. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 2005; 307:593-596.
14. Zhou D, Li P, Lin Y, et al. Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens. Immunity 2005; 22:571-581.
15. Jacobson S, Sekaly RP, Jacobson CL, et al. HLA class II-restricted presentation of cytoplasmic measles virus antigens to cytotoxic T cells. J Virol 1989; 63:1756-1762.
16. Jaraquemada D, Marti M, Long EO. An endogenous processing pathway in vaccinia virus-infected cells for presentation of cytoplasmic antigens to class II-restricted T cells. J Exp Med 1990; 172:947-954.
17. Wang RF, Wang X, Atwood AC, et al. Cloning genes encoding MHC class IIrestricted antigens: mutated CDC27 as a tumor antigen. Science 1999; 284:1351-1354.
18. Gratwohl A, Dohler B, Stern M, Opelz G. H-Y as a minor histocompatibility antigen in kidney transplantation: a retrospective cohort study. Lancet 2008; 372:49-53.
19. Dierselhuis M, Goulmy E. The relevance of minor histocompatibility antigens in solid organ transplantation. Curr Opin Organ Transplant 2009; 14:419-425.
20. Spierings E, Drabbels J, Hendriks M, et al. A uniform genomic minor histocompatibility antigen typing methodology and database designed to facilitate clinical applications. PLoS One 2006; 1:e42.
21. Frank S. Dynamics of cancer. Princeton, NJ: Princeton University Press; 2007.
22. Frank SA. Evolution in health and medicine Sackler colloquium: somatic evolutionary genomics: mutations during development cause highly variable genetic mosaicism with risk of cancer and neurodegeneration. Proc Natl Acad Sci U S A 2010; 107 (Suppl 1):1725-1730.
23. Sterns S, Koella J. Evolution in health and disease. Oxford, UK: Oxford University Press; 2008.
24. Dronamraju K. Infectious diseases and host-pathogen evolution. Cambridge, UK: Cambridge University Press; 2004.
25. Zhang F, Gu W, Hurles ME, Lupski JR. Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet 2009; 10:451-481.
26. Fanciulli M, Norsworthy PJ, Petretto E, et al. FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nat Genet 2007; 39:721-723.
27. Bruder CE, Piotrowski A, Gijsbers AA, et al. Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am J Hum Genet 2008; 82:763-771.
28. Gringras P, Chen W. Mechanisms for differences in monozygous twins. Early Hum Dev 2001; 64:105-117.
29. Duret L, Galtier N. Biased gene conversion and the evolution of mammalian genomic landscapes. Annu Rev Genomics Hum Genet 2009; 10:285-311.
30. Weinshilboum RM, Wang L. Pharmacogenetics and pharmacogenomics: development, science, and translation. Annu Rev Genomics Hum Genet 2006; 7:223-245.
31. Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature 2009; 457:480-484.
32. Turnbaugh PJ, Quince C, Faith JJ, et al. Organismal, genetic, and transcriptional variation in the deeply sequenced gut microbiomes of identical twins. Proc Natl Acad Sci U S A 2010; 107:7503-7508.
33. Clayton TA, Baker D, Lindon JC, et al. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc Natl Acad Sci U S A 2009; 106:14728-14733.
34. Wilson ID, Nicholson JK. The role of gut microbiota in drug response. Curr Pharm Des 2009; 15:1519-1523.
35. Kloetzel PM. Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII. Nat Immunol 2004; 5:661-669.
36. Malarkannan S, Shih PP, Eden PA, et al. The molecular and functional characterization of a dominant minor H antigen, H60. J Immunol 1998; 161:3501-3509.
37. Luedtke B, Pooler LM, Choi EY, et al. A single nucleotide polymorphism in the Emp3 gene defines the H4 minor histocompatibility antigen. Immunogenetics 2003; 55:284-295.
38. Yadav R, Yoshimura Y, Boesteanu A, et al. The H4b minor histocompatibility antigen is caused by a combination of genetically determined and posttranslational modifications. J Immunol 2003; 170:5133-5142.
39. Malarkannan S, Horng T, Eden P, et al. Differences that matter: major cytotoxic T cell-stimulating minor histocompatibility antigens. Immunity 2000; 13:333-344.
40. Zuberi AR, Christianson GJ, Mendoza LM, et al. Positional cloning and molecular characterization of an immunodominant cytotoxic determinant of the mouse H3 minor histocompatibility complex. Immunity 1998; 9:687-698.
41. Eden PA, ChristiansonGJ, Fontaine P, et al. Biochemical and immunogenetic analysis of an immunodominant peptide (B6dom1) encoded by the classical H7 minor histocompatibility locus. J Immunol 1999; 162:4502-4510.
42. McBride K, Baron C, Picard S, et al. The model B6(dom1) minor histocompatibility antigen is encoded by a mouse homolog of the yeast STT3 gene. Immunogenetics 2002; 54:562-569.
43. Mendoza LM, Paz P, Zuberi A, et al. Minors held by majors: the H13 minor histocompatibility locus defined as a peptide/MHC class I complex. Immunity 1997; 7:461-472.
44. Mendoza LM, Villaflor G, Eden P, et al. Distinguishing self from nonself: immunogenicity of the murine H47 locus is determined by a single amino acid substitution in an unusual peptide. J Immunol 2001; 166:4438-4445.
45. Greenfield A, Scott D, Pennisi D, et al. An H-YDb epitope is encoded by a novel mouse Y chromosome gene. Nat Genet 1996; 14:474-478.
46. Millrain M, Scott D, Addey C, et al. Identification of the immunodominant HY H2-D(k) epitope and evaluation of the role of direct and indirect antigen presentation in HY responses. J Immunol 2005; 175:7209-7217.
47. Scott DM, Ehrmann IE, Ellis PS, et al. Identification of a mouse male-specific transplantation antigen, H-Y. Nature 1995; 376:695-698.
48. den Haan JM, Meadows LM, Wang W, et al. The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymorphism. Science 1998; 279:1054-1057.
49. Mommaas B, Kamp J, Drijfhout JW, et al. Identification of a novel HLA-B60- restricted T cell epitope of the minor histocompatibility antigen HA-1 locus. J Immunol 2002; 169:3131-3136.
50. den Haan JM, Sherman NE, Blokland E, et al. Identification of a graft versus host disease-associated human minor histocompatibility antigen. Science 1995; 268:1476-1480.
51. Spierings E, Brickner AG, Caldwell JA, et al. The minor histocompatibility antigen HA-3 arises from differential proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein. Blood 2003; 102:621-629.
52. Brickner AG, Warren EH, Caldwell JA, et al. The immunogenicity of a new human minor histocompatibility antigen results from differential antigen processing. J Exp Med 2001; 193:195-206.
53. Dolstra H, Fredrix H, Maas F, et al. A human minor histocompatibility antigen specific for B cell acute lymphoblastic leukemia. J Exp Med 1999; 189:301-308.
54. Akatsuka Y, Nishida T, Kondo E, et al. Identification of a polymorphic gene, BCL2A1, encoding two novel hematopoietic lineage-specific minor histocompatibility antigens. J Exp Med 2003; 197:1489-1500.
55. McCarroll SA, Bradner JE, Turpeinen H, et al. Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease. Nat Genet 2009; 41:1341-1344.
56. Terakura S, Murata M, Warren EH, et al. A single minor histocompatibility antigen encoded by UGT2B17 and presented by human leukocyte antigen- A2902 and -B4403. Transplantation 2007; 83:1242-1248.
57. de Rijke B, van Horssen-Zoetbrood A, Beekman JM, et al. A frameshift polymorphism in P2X5 elicits an allogeneic cytotoxic T lymphocyte response associated with remission of chronic myeloid leukemia. J Clin Invest 2005; 115:3506-3516.
58. Warren EH, Vigneron NJ, Gavin MA, et al. An antigen produced by splicing of noncontiguous peptides in the reverse order. Science 2006; 313:1444-1447.
59. Brickner AG, Evans AM, Mito JK, et al. The PANE1 gene encodes a novel human minor histocompatibility antigen that is selectively expressed in B-lymphoid cells and B-CLL. Blood 2006; 107:3779-3786.
60. Tykodi SS, Fujii N, Vigneron N, et al. C19orf48 encodes a minor histocompatibility antigen recognized by CD8+ cytotoxic T cells from renal cell carcinoma patients. Clin Cancer Res 2008; 14:5260-5269.
61. Slager EH, Honders MW, van der Meijden ED, et al. Identification of the angiogenic endothelial-cell growth factor-1/thymidine phosphorylase as a potential target for immunotherapy of cancer. Blood 2006; 107:4954-4960.
62. Torikai H, Akatsuka Y, Miyazaki M, et al. The human cathepsin H gene encodes two novel minor histocompatibility antigen epitopes restricted by HLA-A3101 and -A3303. Br J Haematol 2006; 134:406-416.
63. van Bergen CA, Kester MG, Jedema I, et al. Multiple myeloma-reactive T cells recognize an activation-induced minor histocompatibility antigen encoded by the ATP-dependent interferon-responsive (ADIR) gene. Blood 2007; 109:4089-4096.
64. Kawase T, Akatsuka Y, Torikai H, et al. Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen. Blood 2007; 110:1055-1063.
65. Pierce RA, Field ED, den Haan JM, et al. Cutting edge: the HLA-A0101- restricted HY minor histocompatibility antigen originates from DFFRY and contains a cysteinylated cysteine residue as identified by a novel mass spectrometric technique. J Immunol 1999; 163:6360-6364.
66. Vogt MH, de Paus RA, Voogt PJ, et al. DFFRY codes for a new human malespecific minor transplantation antigen involved in bone marrow graft rejection. Blood 2000; 95:1100-1105.
67. Meadows L, Wang W, den Haan JM, et al. The HLA-A0201-restricted H-Y antigen contains a posttranslationally modified cysteine that significantly affects T cell recognition. Immunity 1997; 6:273-281.
68. Torikai H, Akatsuka Y, Miyazaki M, et al. A novel HLA-A3303-restricted minor histocompatibility antigen encoded by an unconventional open reading frame of human TMSB4Y gene. J Immunol 2004; 173:7046-7054.
69. Wang W, Meadows LR, den Haan JM, et al. Human H-Y: a male-specific histocompatibility antigen derived from the SMCY protein. Science 1995; 269:1588-1590.
70. Warren EH, Gavin MA, Simpson E, et al. The human UTY gene encodes a novel HLA-B8-restricted H-Y antigen. J Immunol 2000; 164:2807-2814.
71. Ivanov R, Aarts T, Hol S, et al. Identification of a 40S ribosomal protein S4-derived H-Y epitope able to elicit a lymphoblast-specific cytotoxic T lymphocyte response. Clin Cancer Res 2005; 11:1694-1703.
72. Vogt MH, Goulmy E, Kloosterboer FM, et al. UTY gene codes for an HLAB60- restricted human male-specific minor histocompatibility antigen involved in stem cell graft rejection: characterization of the critical polymorphic amino acid residues for T-cell recognition. Blood 2000; 96:3126-3132.
73. Vigneron N, Stroobant V, Chapiro J, et al. An antigenic peptide produced by peptide splicing in the proteasome. Science 2004; 304:587-590.
74. Shepherd JC, Schumacher TN, Ashton-Rickardt PG, et al. TAP1-dependent peptide translocation in vitro is ATP dependent and peptide selective. Cell 1993; 74:577-584.
75. Heemels MT, Schumacher TN, Wonigeit K, Ploegh HL. Peptide translocation by variants of the transporter associated with antigen processing. Science 1993; 262:2059-2063.
76. Hammer GE, Gonzalez F, Champsaur M, et al. The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules. Nat Immunol 2006; 7:103-112.
77. Yan J, Parekh VV, Mendez-Fernandez Y, et al. In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules. J Exp Med 2006; 203:647-659.
78. York IA, Chang SC, Saric T, et al. The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues. Nat Immunol 2002; 3:1177-1184.
79. Serwold T, Gaw S, Shastri N. ER aminopeptidases generate a unique pool of peptides for MHC class I molecules. Nat Immunol 2001; 2:644-651.
80. Serwold T, Gonzalez F, Kim J, et al. ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum. Nature 2002; 419:480-483.
81. Saveanu L, Carroll O, Lindo V, et al. Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat Immunol 2005; 6:689-697.
82. Bird PI, Trapani JA, Villadangos JA. Endolysosomal proteases and their inhibitors in immunity. Nat Rev Immunol 2009; 9:871-882.
83. Heath WR, Carbone FR. Cross-presentation, dendritic cells, tolerance and immunity. Annu Rev Immunol 2001; 19:47-64.
84. Reed AJ, Noorchashm H, Rostami SY, et al. Alloreactive CD4 T cell activation in vivo: an autonomous function of the indirect pathway of alloantigen presentation. J Immunol 2003; 171:6502-6509.
85. Richards DM, Dalheimer SL, Ehst BD, et al. Indirect minor histocompatibility antigen presentation by allograft recipient cells in the draining lymph node leads to the activation and clonal expansion of CD4+ T cells that cause obliterative airways disease. J Immunol 2004; 172:3469-3479.
86. Tewari MK, Sinnathamby G, Rajagopal D, Eisenlohr LC. A cytosolic pathway for MHC class II-restricted antigen processing that is proteasome and TAP dependent. Nat Immunol 2005; 6:287-294.
87. Ackerman AL, Giodini A, Cresswell P. A role for the endoplasmic reticulum protein retrotranslocation machinery during crosspresentation by dendritic cells. Immunity 2006; 25:607-617.
88. Sahara H, Shastri N. Second class minors: molecular identification of the autosomal H46 histocompatibility locus as a peptide presented by major histocompatibility complex class II molecules. J Exp Med 2003; 197:375-385.
89. Scott D, Addey C, Ellis P, et al. Dendritic cells permit identification of genes encoding MHC class II-restricted epitopes of transplantation antigens. Immunity 2000; 12:711-720.
90. Spaapen RM, Lokhorst HM, van den Oudenalder K, et al. Toward targeting B cell cancers with CD4+ CTLs: identification of a CD19-encoded minor histocompatibility antigen using a novel genome-wide analysis. J Exp Med 2008; 205:2863-2872.
91. Vogt MH, van den Muijsenberg JW, Goulmy E, et al. The DBY gene codes for an HLA-DQ5-restricted human male-specific minor histocompatibility antigen involved in graft-versus-host disease. Blood 2002; 99:3027-3032.
92. Zorn E, Miklos DB, Floyd BH, et al. Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation. J Exp Med 2004; 199:1133-1142.
93. Spierings E, Vermeulen CJ, Vogt MH, et al. Identification of HLA class IIrestricted H-Y-specific T-helper epitope evoking CD4+ T-helper cells in H-Ymismatched transplantation. Lancet 2003; 362:610-615.
94. Ruppert J, Sidney J, Celis E, et al. Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell 1993; 74:929-937.
95. Theodossis A, Guillonneau C, Welland A, et al. Constraints within major histocompatibility complex class I restricted peptides: presentation and consequences for T-cell recognition. Proc Natl Acad Sci U S A 2010; 107:5534-5539.
96. Brown JH, Jardetzky TS, Gorga JC, et al. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 1993; 364:33-39.
97. McFarland BJ, Sant AJ, Lybrand TP, Beeson C. Ovalbumin (323-339) peptide binds to the major histocompatibility complex class II I-Ad protein using two functionally distinct registers. Biochemistry 1999; 38:16663-16670.
98. Landais E, Romagnoli PA, Corper AL, et al. New design of MHC class II tetramers to accommodate fundamental principles of antigen presentation. J Immunol 2010; 183:7949-7957.
99. Li Y, Li H, Martin R, Mariuzza RA. Structural basis for the binding of an immunodominant peptide from myelin basic protein in different registers by two HLA-DR2 proteins. J Mol Biol 2000; 304:177-188.
100. Boesteanu A, Brehm M, Mylin LM, et al. A molecular basis for how a single TCR interfaces multiple ligands. J Immunol 1998; 161:4719-4727.
101. Huseby ES, White J, Crawford F, et al. How the T cell repertoire becomes peptide and MHC specific. Cell 2005; 122:247-260.
102. Rudolph MG, Stanfield RL, Wilson IA. How TCRs bind MHCs, peptides, and coreceptors. Annu Rev Immunol 2006; 24:419-466.
103. Burrows SR, Chen Z, Archbold JK, et al. Hard wiring of the T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptibility. Proc Natl Acad Sci U S A 2010; 106:doi/10.1073/pnas. 1004926107.
104. Tynan FE, Burrows SR, Buckle AM, et al. T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I-bound peptide. Nat Immunol 2005; 6:1114-1122.
105. Tynan FE, Reid HH, Kjer-Nielsen L, 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.
106. Marrack P, Scott-Browne JP, Dai S, et al. Evolutionarily conserved amino acids that control TCR-MHC interaction. Annu Rev Immunol 2008; 26:171-203.
107. Feng D, Bond CJ, Ely LK, et al. Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'. Nat Immunol 2005; 8:975-983.
108. Yin Y, Mariuzza RA. The multiple mechanisms of T cell receptor crossreactivity. Immunity 2009; 31:849-851.
109. Degano M, Garcia KC, Apostolopoulos V, et al. A functional hot spot for antigen recognition in a superagonist TCR/MHC complex. Immunity 2000; 12:251-261.
110. Garcia KC, Degano M, Pease LR, et al. Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science 1998; 279:1166-1172.
111. Garcia KC, Degano M, Stanfield RL, et al. An alphabeta T cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex. Science 1996; 274:209-219.
112. Mazza C, Auphan-Anezin N, Gregoire C, et al. How much can a T-cell antigen receptor adapt to structurally distinct antigenic peptides? EMBO J 2007; 26:1972-1983.
113. Reiser JB, Darnault C, Gregoire C, et al. CDR3 loop flexibility contributes to the degeneracy of TCR recognition. Nat Immunol 2003; 4:241-247.
114. Reiser JB, Darnault C, Guimezanes A, et al. Crystal structure of a T cell receptor bound to an allogeneic MHC molecule. Nat Immunol 2000; 1:291-297.
115. Li Y, Huang Y, Lue J, 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 2005; 24:2968-2979.
116. Macdonald WA, Chen Z, Gras S, et al. T cell allorecognition via molecular mimicry. Immunity 2009; 31:897-908.
117. Harkiolaki M, Holmes SL, Svendsen P, et al. T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. Immunity 2009; 30:348-357.
118. Borbulevych OY, Piepenbrink KH, Gloor BE, et al. T cell receptor crossreactivity directed by antigen-dependent tuning of peptide-MHC molecular flexibility. Immunity 2009; 31:885-896.
119. Rock KL, Latz E, Ontiveros F, Kono H. The sterile inflammatory response. Annu Rev Immunol 2010; 28:321-342.
120. Medzhitov R. Origin and physiological roles of inflammation. Nature 2008; 454:428-435.
121. Hornung V, Bauernfeind F, Halle A, et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 2008; 9:847-856.
122. Duewell P, Kono H, Rayner KJ, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 2010; 464:1357-1361.
123. Halle A, Hornung V, Petzold GC, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol 2008; 9:857-865.
124. Hess PR, Barnes C, WoolardMD, et al. Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosomeinactivating protein saporin. Blood 2007; 109:3300-3307.
125. Soen Y, Chen DS, Kraft DL, et al. Detection and characterization of cellular immune responses using peptide-MHC microarrays. PLoS Biol 2003; 1:E65.
126. Stone JD, Demkowicz WE Jr, Stern LJ. HLA-restricted epitope identification and detection of functional T cell responses by using MHC-peptide and costimulatory microarrays. Proc Natl Acad Sci U S A 2005; 102:3744-3749.
127. Hadrup SR, Bakker AH, Shu CJ, et al. Parallel detection of antigen-specific Tcell responses by multidimensional encoding of MHC multimers. Nat Methods 2009; 6:520-526.
128. Moon JJ, Chu HH, Pepper M, et al. Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity 2007; 27:203-213.
129. Jenkins MK, Chu HH, McLachlan JB, Moon JJ. On the composition of the preimmune repertoire of T cells specific for peptide-major histocompatibility complex ligands. Annu Rev Immunol 2010; 28:275-294.
130. Choi EY, Christianson GJ, Yoshimura Y, et al. Immunodominance of H60 is caused by an abnormally high precursor T cell pool directed against its unique minor histocompatibility antigen peptide. Immunity 2002; 17:593-603.
131. Vincent BG, Young EF, Buntzman AS, et al. Toxin-coupled MHC class I tetramers can specifically ablate autoreactive CD8+ T cells and delay diabetes in nonobese diabetic mice. J Immunol 2010; 184:4196-4204.