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Autoimmune disease: why and where it occurs

Abstract

Autoimmune disease is controlled by genetic and environmental factors. Both of these affect susceptibility to autoimmunity at three levels: the overall reactivity of the immune system, the specific antigen and its presentation, and the target issue.

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Figure 1
Figure 2: Chromosomal regions linked with autoimmune diseases.

References

  1. Jacobson, D.L., Gange, S.J., Rose, N.R. & Graham, N.M. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin. Immunol. Immunopathol. 84, 223–243 (1997).

    Article  CAS  PubMed  Google Scholar 

  2. Mathews, M.B. & Bernstein, R.M. Myositis autoantibody inhibits histidyl-tRNA synthetase: A model for autoimmunity. Nature 304, 177–179 (1983).

    Article  CAS  PubMed  Google Scholar 

  3. Yeaman, S.J. et al. Primary biliary cirrhosis: Identification of two major M2 mitochondrial autoantigens. Lancet 1, 1067–1070 (1988).

    Article  CAS  PubMed  Google Scholar 

  4. Matsumoto, I., Staub, A., Benoist, C. & Mathis, D. Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme. Science 286, 1732–1735 (1999).

    Article  CAS  PubMed  Google Scholar 

  5. Steinman, L. Multiple sclerosis: A coordinated immunological attack against myelin in the central nervous system. Cell 85, 299–302 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Hutchings, P., O'Reilly, L., Parish, N.M., Waldmann, H. & Cooke, A. The use of a non-depleting anti-CD4 monoclonal antibody to re-establish tolerance to β cells in NOD mice. Eur J. Immunol. 22, 1913–1918 (1992).

    Article  CAS  PubMed  Google Scholar 

  7. Wong, F.S., Visintin, I., Wen, L., Flavell, R.A. & Janeway, C.A. Jr. CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells. J. Exp. Med. 183, 67–76 (1996).

    Article  CAS  PubMed  Google Scholar 

  8. Haskins, K. & McDuffie, M. Acceleration of diabetes in young NOD mice with a CD4+ islet-specific T cell clone. Science 249, 1433–1436 (1990).

    Article  CAS  PubMed  Google Scholar 

  9. Yu, L. et al. Antiislet autoantibodies usually develop sequentially rather than simultaneously. J. Clin. Endocrinol. Metab. 81, 4264–4267 (1996).

    CAS  PubMed  Google Scholar 

  10. Kotzin, B.L. Systemic lupus erythematosus. Cell 85, 303–306 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Kotzin, B.L. et al. Use of soluble peptide-DR4 tetramers to detect synovial T cells specific for cartilage antigens in patients with rheumatoid arthritis. Proc. Natl. Acad. Sci. USA 97, 291–296 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nakamura, R.M. Progress in the use of biochemical and biological markers for evaluation of rheumatoid arthritis. J. Clin. Lab. Anal. 14, 305–313 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Shamim, E.A. & Miller, F.W. Familial autoimmunity and the idiopathic inflammatory myopathies. Curr. Rheumatol. Rep. 2, 201–211 (2000).

    Article  CAS  PubMed  Google Scholar 

  14. Verge, C. & Eisenbarth, G.S. Autocrine polyendocrine syndromes. in Williams Textbook of Endocrinology, 9th ed. (eds. Wilson, J.D. & Forster, D.W.) (W.B. Saunders, Philadelphia, 1992).

    Google Scholar 

  15. Bernard, N.F., Ertug, F. & Margolese, H. High incidence of thyroiditis and anti-thyroid autoantibodies in NOD mice. Diabetes 41, 40–46 (1992).

    Article  CAS  PubMed  Google Scholar 

  16. Vyse, T.J. & Kotzin, B.L. Genetic susceptibility to systemic lupus erythematosus. Annu. Rev. Immunol. 16, 261–292 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Theofilopoulos, A.N. & Kono, D.H. The genes of systemic autoimmunity. Proc. Assoc. Am. Physicians 111, 228–240 (1999).

    Article  CAS  PubMed  Google Scholar 

  18. Wakeland, E.K., Wandstrat, A.E., Liu, K. & Morel, L. Genetic dissection of systemic lupus erythematosus. Curr. Opin. Immunol. 11, 701–707 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Harley, J.B., Moser, K.L., Gaffney, P.M. & Behrens, T.W. The genetics of human systemic lupus erythematosus. Curr. Opin. Immunol. 10, 690–696 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. Griffiths, M.M., Encinas, J.A., Remmers, E.F., Kuchroo, V.K. & Wilder, R.L. Mapping autoimmunity genes. Curr. Opin. Immunol. 11, 689–700 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. Encinas, J.A. & Kuchroo, V.K. Mapping and identification of autoimmunity genes. Curr. Opin. Immunol. 12, 691–697 (2000).

    Article  CAS  PubMed  Google Scholar 

  22. Becker, K.G. et al. Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases. Proc. Natl. Acad. Sci. USA 95, 9979–9984 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bergsteinsdottir, K., Yang, H.T., Pettersson, U. & Holmdahl, R. Evidence for common autoimmune disease genes controlling onset, severity, and chronicity based on experimental models for multiple sclerosis and rheumatoid arthritis. J. Immunol. 164, 1564–1568 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Vyse, T.J. & Todd, J.A. Genetic analysis of autoimmune disease. Cell 85; 311–318 (1996)

    Article  CAS  PubMed  Google Scholar 

  25. Bell, J.I. & Lathrop, G.M. Multiple loci for multiple sclerosis. Nature Genet. 13, 377–378 (1996).

    Article  CAS  PubMed  Google Scholar 

  26. Jawaheer, D. et al. A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases. Am. J. Hum. Genet. 68, 927–936 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Encinas, J.A. et al. QTL influencing autoimmune diabetes and encephalomyelitis map to a 0.15-cM region containing Il2. Nature Genet. 21, 158–160 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. Donner, H. et al. Codon 17 polymorphism of the cytotoxic T lymphocyte antigen 4 gene in Hashimoto's thyroiditis and Addison's disease. J. Clin. Endocrinol. Metab. 82, 4130–4132 (1997).

    CAS  PubMed  Google Scholar 

  29. Holopainen, P. et al. CD28/CTLA4 gene region on chromosome 2q33 confers genetic susceptibility to celiac disease. A linkage and family-based association study. Tissue Antigens 53, 470–475 (1999).

    Article  CAS  PubMed  Google Scholar 

  30. Nagamine, K. et al. Positional cloning of the APECED gene. Nature Genet. 17, 393–398 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Horak, I., Lohler, J., Ma, A. & Smith, K.A. Interleukin-2 deficient mice: A new model to study autoimmunity and self-tolerance. Immunol. Rev. 148, 35–44 (1995).

    Article  CAS  PubMed  Google Scholar 

  32. Boillot, D., Assan, R., Dardenne, M., Debray-Sachs, M. & Bach, J.F. T-lymphopenia and T-cell imbalance in diabetic db/db mice. Diabetes 35, 198–203 (1986).

    Article  CAS  PubMed  Google Scholar 

  33. Bellgrau, D. & Lagarde, A.C. Cytotoxic T-cell precursors with low-level CD8 in the diabetes-prone Biobreeding rat: Implications for generation of an autoimmune T-cell repertoire. Proc. Natl. Acad. Sci. USA 87, 313–317 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yunis, E.J., Fernandes, G. & Greenberg, L.J. Immune deficiency, autoimmunity and aging. Birth Defects Orig. Artic. Ser. 11, 185–192 (1975).

    CAS  PubMed  Google Scholar 

  35. Goodwin, J.S., Searles, R.P. & Tung, K.S. Immunological responses of healthy elderly population. Clin. Exp. Immunol. 48, 403–410 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Sobel, E.S. et al. An intrinsic B cell defect is required for the production of autoantibodies in the lpr model of murine systemic autoimmunity. J. Exp. Med. 173, 1441–1449 (1991).

    Article  CAS  PubMed  Google Scholar 

  37. Strasser, A., Harris, A.W. & Cory, S. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 67, 889–899 (1991).

    Article  CAS  PubMed  Google Scholar 

  38. Bolland, S. & Ravetch, J.V. Spontaneous autoimmune disease in Fc(γ)RIIB-deficient mice results from strain-specific epistasis. Immunity 13, 277–285 (2000).

    Article  CAS  PubMed  Google Scholar 

  39. Khare, S.D. et al. Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. Proc. Natl. Acad. Sci. USA 97, 3370–3375 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Cornall, R.J. et al. Polygenic autoimmune traits: Lyn, CD22 and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection. Immunity 8, 497–508 (1998).

    Article  CAS  PubMed  Google Scholar 

  41. Vyse, T.J., Rozzo, S.J., Drake, C.G., Izui, S. & Kotzin, B.L. Control of multiple autoantibodies linked with a lupus nephritis susceptibility locus in New Zealand black mice. J. Immunol. 158, 5566–5574 (1997).

    CAS  PubMed  Google Scholar 

  42. Sobel, E.S., Mohan, C., Morel, L., Schiffenbauer, J. & Wakeland, E.K. Genetic dissection of SLE pathogenesis: Adoptive transfer of Sle1 mediates the loss of tolerance by bone marrow-derived B cells. J. Immunol. 162, 2415–2421 (1999).

    CAS  PubMed  Google Scholar 

  43. Nepom, G.T. & Kwok, W.W. Molecular basis for HLA-DQ associations with IDDM. Diabetes 47, 1177–1184 (1998).

    Article  CAS  PubMed  Google Scholar 

  44. Nepom, G.T. Major histocompatibility complex-directed susceptibility to rheumatoid arthritis. Adv. Immunol. 68, 315–332 (1998).

    Article  CAS  PubMed  Google Scholar 

  45. Stratmann, T. et al. The I-Ag7 MHC class II molecule linked to murine diabetes is a promiscuous peptide binder. J. Immunol. 165, 3214–3225 (2000).

    Article  CAS  PubMed  Google Scholar 

  46. Carrasco-Marin, E., Shimizu, J., Kanagawa, O. & Unanue, E.R. The class II MHC I-Ag7 molecules from non-obese diabetic mice are poor peptide binders. J. Immunol. 156, 450–458 (1996).

    CAS  PubMed  Google Scholar 

  47. Rasooly, L., Burek, C.L. & Rose, N.R. Iodine-induced autoimmune thyroiditis in NOD-H-2h4 mice. Clin. Immunol. Immunopathol. 81, 287–292 (1996).

    Article  CAS  PubMed  Google Scholar 

  48. Bennett, S.T. et al. Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. Nature Genet. 9, 284–292 (1995).

    Article  CAS  PubMed  Google Scholar 

  49. Vafiadis, P. et al. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Nature Genet. 15, 289–292 (1997).

    Article  CAS  PubMed  Google Scholar 

  50. Klein, L., Klugmann, M., Nave, K.A., Tuohy, V.K. & Kyewski, B. Shaping of the autoreactive T-cell repertoire by a splice variant of self protein expressed in thymic epithelial cells. Nature Med. 6, 56–61 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Anderson, A.C. et al. High frequency of autoreactive myelin proteolipid protein-specific T cells in the periphery of naive mice: Mechanisms of selection of the self-reactive repertoire. J. Exp. Med. 191, 761–770 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Botto, M. et al. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nature Genet. 19, 56–59 (1998).

    Article  CAS  PubMed  Google Scholar 

  53. Slingsby, J.H. et al. Homozygous hereditary C1q deficiency and systemic lupus erythematosus. A new family and the molecular basis of C1q deficiency in three families. Arthritis Rheum. 39, 663–670 (1996).

    Article  CAS  PubMed  Google Scholar 

  54. Streilein, J.W., Wilbanks, G.A. & Cousins, S.W. Immunoregulatory mechanisms of the eye. J. Neuroimmunol. 39, 185–200 (1992).

    Article  CAS  PubMed  Google Scholar 

  55. Griffith, T.S., Brunner, T., Fletcher, S.M., Green, D.R. & Ferguson, T.A. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 270, 1189–1192 (1995).

    Article  CAS  PubMed  Google Scholar 

  56. Salmon, J.E. et al. Fc-γ RIIA alleles are heritable risk factors for lupus nephritis in African Americans. J. Clin. Invest. 97, 1348–1354 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wu, J. et al. A novel polymorphism of FcγRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. J. Clin. Invest. 100, 1059–1070 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Clynes, R., Dumitru, C. & Ravetch, J.V. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis. Science 279, 1052–1054 (1998).

    Article  CAS  PubMed  Google Scholar 

  59. Vyse, T.J. et al. Genetic linkage of IgG autoantibody production in relation to lupus nephritis in New Zealand hybrid mice. J. Clin. Invest. 98, 1762–1772 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kuan, A.P. et al. Genetic control of autoimmune myocarditis mediated by myosin-specific antibodies. Immunogenetics 49, 79–85 (1999).

    Article  CAS  PubMed  Google Scholar 

  61. Chiller, J.M., Skidmore, B.J., Morrison, D.C. & Weigle, W.O. Relationship of the structure of bacterial lipopolysaccharides to its function in mitogenesis and adjuvanticity. Proc. Natl. Acad. Sci. USA 70, 2129–2133 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kearney, E.R., Pape, K.A., Loh, D.Y. & Jenkins, M.K. Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. Immunity 1, 327–339 (1994).

    Article  CAS  PubMed  Google Scholar 

  63. Vella, A.T. et al. CD28 engagement and proinflammatory cytokines contribute to T cell expansion and long-term survival in vivo. J. Immunol. 158, 4714–4720 (1997).

    CAS  PubMed  Google Scholar 

  64. Tanaka, H., Demeure, C.E., Rubio, M., Delespesse, G. & Sarfati, M. Human monocyte-derived dendritic cells induce naive T cell differentiation into T helper cell type 2 (Th2) or Th1/Th2 effectors. Role of stimulator/responder ratio. J. Exp. Med. 192, 405–412 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Cumberbatch, M. & Kimber, I. Tumour necrosis factor-α is required for accumulation of dendritic cells in draining lymph nodes and for optimal contact sensitization. Immunology 84, 31–35 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Segal, B.M., Klinman, D.M. & Shevach, E.M. Microbial products induce autoimmune disease by an IL-12-dependent pathway. J. Immunol. 158, 5087–5090 (1997).

    CAS  PubMed  Google Scholar 

  67. Brackertz, D., Mitchell, G.F. & Mackay, I.R. Antigen-induced arthritis in mice. I. Induction of arthritis in various strains of mice. Arthritis Rheum. 20, 841–850 (1977).

    Article  CAS  PubMed  Google Scholar 

  68. Esquivel, P.S., Rose, N.R. & Kong, Y.C. Induction of autoimmunity in good and poor responder mice with mouse thyroglobulin and lipopolysaccharide. J. Exp. Med. 145, 1250–1263 (1977).

    Article  CAS  PubMed  Google Scholar 

  69. Lucey, D.R., Clerici, M. & Shearer, G.M. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin. Microbiol. Rev. 9, 532–562 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sher, A. et al. Cytokines as determinants of disease and disease interactions. Braz. J. Med. Biol. Res. 31, 85–87 (1998).

    Article  CAS  PubMed  Google Scholar 

  71. Romagnani, S. Th1/Th2 cells. Inflamm. Bowel Dis. 5, 285–94 (1999).

    Article  CAS  PubMed  Google Scholar 

  72. Theofilopoulos, A.N. & Lawson, B.R. Tumour necrosis factor and other cytokines in murine lupus. Ann. Rheum. Dis. 58 (Suppl. 1), I49–55 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Gross, D.M. et al. Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis. Science 281, 703–706 (1998).

    Article  CAS  PubMed  Google Scholar 

  74. Dell, A. et al. Autoimmune determinants of rheumatic carditis: Localization of epitopes in human cardiac myosin. Eur. Heart J. 12 (Suppl. D), 158–62 (1991).

    Article  PubMed  Google Scholar 

  75. Schloot, N.C. et al. Molecular mimicry in type 1 diabetes mellitus revisited: T-cell clones to GAD65 peptides with sequence homology to Coxsackie or proinsulin peptides do not crossreact with homologous counterpart. Hum. Immunol. 62, 299–309 (2001).

    Article  CAS  PubMed  Google Scholar 

  76. Davies, J.M. Molecular mimicry: Can epitope mimicry induce autoimmune disease? Immunol. Cell Biol. 75, 113–126 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ringrose, J.H. HLA-B27 associated spondyloarthropathy, an autoimmune disease based on crossreactivity between bacteria and HLA-B27? Ann. Rheum. Dis. 58, 598–610 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Jakobiec, F.A., Lefkowitch, J. & Knowles, D.M., 2nd. B- and T-lymphocytes in ocular disease. Ophthalmology 91, 635–654 (1984).

    Article  CAS  PubMed  Google Scholar 

  79. Konno, N., Makita, H., Yuri, K., Iizuka, N. & Kawasaki, K. Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan. J. Clin. Endocrinol. Metab. 78, 393–397 (1994).

    CAS  PubMed  Google Scholar 

  80. Miller, S.D. et al. Persistent infection with Theiler's virus leads to CNS autoimmunity via epitope spreading. Nature Med. 3, 1133–1136 (1997).

    Article  CAS  PubMed  Google Scholar 

  81. Mach, F. et al. Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: Implications for CD40–CD40 ligand signaling in atherosclerosis. Proc. Natl. Acad. Sci. USA 94, 1931–1936 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hogaboam, C.M., Snider, D.P. & Collins, S.M. Cytokine modulation of T-lymphocyte activation by intestinal smooth muscle cells. Gastroenterology 112, 1986–1995 (1997).

    Article  CAS  PubMed  Google Scholar 

  83. Seko, Y. et al. Expression of costimulatory molecule CD40 in murine heart with acute myocarditis and reduction of inflammation by treatment with anti-CD40L/B7-1 monoclonal antibodies. Circ. Res. 83, 463–469 (1998).

    Article  CAS  PubMed  Google Scholar 

  84. Poltorak, A. et al. Genetic and physical mapping of the Lps locus: Identification of the toll-4 receptor as a candidate gene in the critical region. Blood Cells Mol. Dis. 24, 340–355 (1998).

    Article  CAS  PubMed  Google Scholar 

  85. Locksley, R.M. et al. Development of CD4+ effector T cells and susceptibility to infectious diseases. Adv Exp. Med. Biol. 452, 45–52 (1998).

    Article  CAS  PubMed  Google Scholar 

  86. Cook, H.B. et al. Adult coeliac disease: Prevalence and clinical significance. J. Gastroenterol Hepatol. 15, 1032–1036 (2000).

    Article  CAS  PubMed  Google Scholar 

  87. Kennedy, N.P. & Feighery, C. Clinical features of coeliac disease today. Biomed. Pharmacother. 54, 373–380 (2000).

    Article  CAS  PubMed  Google Scholar 

  88. Edelson, R.L. Pemphigus—decoding the cellular language of cutaneous autoimmunity. N. Engl. J. Med. 343, 60–61 (2000).

    Article  CAS  PubMed  Google Scholar 

  89. Quayle, A.J. et al. Peptide recognition, T cell receptor usage and HLA restriction elements of human heat-shock protein (hsp) 60 and mycobacterial 65-kDa hsp-reactive T cell clones from rheumatoid synovial fluid. Eur J. Immunol. 22, 1315–1322 (1992).

    Article  CAS  PubMed  Google Scholar 

  90. Ufret-Vincenty, R.L. et al. In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis. J. Exp. Med. 188, 1725–1738 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kukreja, A. & Maclaren, N.K. Current cases in which epitope mimicry is considered as a component cause of autoimmune disease: Immune-mediated (type 1) diabetes. Cell. Mol. Life Sci. 57, 534–541 (2000).

    Article  CAS  PubMed  Google Scholar 

  92. Hiemstra, H.S. et al. Cytomegalovirus in autoimmunity: T cell crossreactivity to viral antigen and autoantigen glutamic acid decarboxylase. Proc. Natl. Acad. Sci. USA 98, 3988–3991 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Shimoda, S. et al. Mimicry peptides of human PDC-E2 163–176 peptide, the immunodominant T-cell epitope of primary biliary cirrhosis. Hepatology 31, 1212–1216 (2000).

    Article  CAS  PubMed  Google Scholar 

  94. Albani, S., Tuckwell, J.E., Esparza, L., Carson, D.A. & Roudier, J. The susceptibility sequence to rheumatoid arthritis is a cross-reactive B cell epitope shared by the Escherichia coli heat shock protein dnaJ and the histocompatibility leukocyte antigen DRB10401 molecule. J. Clin. Invest. 89, 327–331 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Albani, S., Carson, D.A. & Roudier, J. Genetic and environmental factors in the immune pathogenesis of rheumatoid arthritis. Rheum. Dis. Clin. North Am. 18, 729–740 (1992).

    CAS  PubMed  Google Scholar 

  96. Wucherpfennig, K.W. & Strominger, J.L. Molecular mimicry in T cell-mediated autoimmunity: Viral peptides activate human T cell clones specific for myelin basic protein. Cell 80, 695–705 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Bachmaier, K. et al. Chlamydia infections and heart disease linked through antigenic mimicry. Science 283, 1335–1339 (1999).

    Article  CAS  PubMed  Google Scholar 

  98. Masuda, M.O. et al. Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked by Trypanosoma cruzi antigens. FASEB J. 12, 1551–1558 (1998).

    Article  CAS  PubMed  Google Scholar 

  99. Schwimmbeck, P.L., Dyrberg, T., Drachman, D.B. & Oldstone, M.B. Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor α-subunit that has biologic activity and reacts immunochemically with herpes simplex virus. J. Clin. Invest. 84, 1174–1180 (1989)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by NIH grants AI-17134, AI-18785, AI-22295 and AR-37070.

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Marrack, P., Kappler, J. & Kotzin, B. Autoimmune disease: why and where it occurs. Nat Med 7, 899–905 (2001). https://doi.org/10.1038/90935

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