Advertisement

HLA and Disease: Molecular Basis

  • Joan C. Gorga
  • Dimitri Monos

Abstract

The central role played by human leukocyte antigens (HLA) in the antigen-specific immune response is well established. Less well established, especially at the molecular level, is the role played by HLA proteins in the wide range of diseases that have been reported to be either positively or negatively associated with the expression of Particular HLA alleles. Major developments in the field of immunology, some, in fact, stimulated by early observations that certain serologically defined HLA alleles were increased in frequency among individuals affected by a particular disease, have now set the scene for rapid progress in defining at the molecular level the roles played by HLA molecules in disease processes. Extensive mapping of the MHC region has identified multiple loci encoding class I and class II HLA proteins, as well as hundreds of genes that encode non-HLA proteins (see chapter 2). Recent developments in tissue typing techniques have enabled HLA typing to move from serological techniques, based on antibody recognition of conformational epitopes on HLA proteins, to DNA-based techniques that depend on allelic sequence differences. As more highly specific antisera have been found and molecular tissue typing techniques have been increasingly used, the initial groupings of class I and class II HLA proteins have been “split” into multiple closely-related alleles, and additional class I and class II alleles have been identified.

Keywords

Major Histocompatibility Complex Human Leukocyte Antigen Major Histocompatibility Complex Class Peptide Binding Human Leukocyte Antigen Class 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bidwell J. Advances in DNA-based HLA-typing methods. Immunol Today 1994; 15: 303–307.CrossRefGoogle Scholar
  2. 2.
    Brewerton D. All About Arthritis. Cambridge: Harvard University Press, 1992.Google Scholar
  3. 3.
    Brewerton DA, Caffrey M, Hart FD et al. Ankylosing spondylitis and HL-B27. Lancet 1973; i:904–907.Google Scholar
  4. 4.
    Schlosstein L, Terasaki PI, Bluestone R et al. High association of HL-A antigen, w27, with ankylosing spondylitis. N Engl J Med 1973; 288: 704–706.CrossRefGoogle Scholar
  5. 5.
    Bodmer JG, Marsh SGE, Albert ED et al. Nomenclature for factors of the HLA system, 1995. Tissue Antigens 1995; 46: 1–18.CrossRefGoogle Scholar
  6. 6.
    Mölders HH, Breuning MH, Ivanyi P et al. Biochemical analysis of variant HLA-B27 antigens. Hum Immunol 1983; 6: 111–117.CrossRefGoogle Scholar
  7. 7.
    Shackelford DA, Mann DL, van Rood JJ et al. Human B cell alloantigens DC1, MT1, and LB12 are identical to each other but distinct from the HLA-DR antigen. Proc Natl Acad Sci USA 1981; 78: 4566–4570.CrossRefGoogle Scholar
  8. 8.
    Lotteau V, Teyton L, Burroughs D et al. A novel HLA class II molecule (DRa-DQB) created by mismatched isotype pairing. Nature 1987; 329: 339–341.CrossRefGoogle Scholar
  9. 9.
    Sollid LM, Markussen G, Ek J et al. Evidence for a primary association of celiac disease to a particular HLA-DQ a/ß heterodimer. J Exp Med 1989; 169: 345–350.CrossRefGoogle Scholar
  10. 10.
    Trucco M. Molecular mechanisms involved in the etiology and pathogenesis of autoimmune diseases. Clin Invest 1992; 70: 756–765.CrossRefGoogle Scholar
  11. 11.
    Luppi P, Rossiello MR, Faas S et al. Genetic background and environment synergistically contribute to the onset of autoimmune diseases. J Mol Med 1995; 73: 381–393.CrossRefGoogle Scholar
  12. 12.
    Sanjeevi CB, Lybrand TP, DeWeese C et al. Polymorphic amino acid variations in HLA-DQ are associated with systemic physical property changes and occurrence of IDDM. Diabetes 1995; 44: 125–131.CrossRefGoogle Scholar
  13. 13.
    Opelz G, Mytilineos J, Scherer S et al. Analysis of HLA-DR matching in DNA-typed cadaver kidney transplants. Transplantation 1993; 55: 782–785.Google Scholar
  14. 14.
    Monos D, Spielman R, Gogolin K et al. The HLA-DQw3.2 allele of the DR4 haplotype is associated with IDDM: Correlation between DQB restriction fragments and DQB chain variation. Immunogenetics 1987; 26: 299–303.CrossRefGoogle Scholar
  15. 14.
    Monos D, Spielman R, Gogolin K et al. The HLA-DQw3.2 allele of the DR4 haplotype is associated with IDDM: Correlation between DQB restriction fragments and DQB chain variation. Immunogenetics 1987; 26: 299–303.CrossRefGoogle Scholar
  16. 16.
    Speiser PW, Dupont B, Rubinstein P et al. High frequency of non classical steroid 21-hydroxylase deficiency. Am J Hum Gen 1985; 37: 650–667.Google Scholar
  17. 17.
    Rich SS, Wilkie PJ, Schut L et al. Spinocerebellar ataxia: localization of an autosomal dominant locus between two markers on human chromosome 6. Am J Hum Genet 1987; 41: 524–531.Google Scholar
  18. 18.
    Toivanen P, Toivanen A, Brines R. When is an autoimmune disease not an autoimmune disease? Immunol Today 1994; 15: 556–559.CrossRefGoogle Scholar
  19. 19.
    Theofilopoulos AN. The basis of autoimmunity: Part I. Mechanisms of aberrant self-recognition. Immunol Today 1995; 16: 90–98.CrossRefGoogle Scholar
  20. 20.
    Theofilopoulos AN. The basis of autoimmunity: Part II. Genetic predisposition. Immunol Today 1995; 16: 150–159.CrossRefGoogle Scholar
  21. 21.
    Rose NR, Bona C. Defining criteria for autoimmune diseases (Witesbky’s postulates revisited.) Immunol Today 1993; 14: 426–430.Google Scholar
  22. 22.
    Bettinotti MP, Hartung K, Deocher HRG et al. DR2 haplotypes (DRB1, DQA1, DQBI) associated with systemic lupus erythematosus. Immunogenetics 1993; 38: 74–77.CrossRefGoogle Scholar
  23. 23.
    Wucherpfennig KW, Strominger JL. Selective binding of self peptides to disease-associated major histocompatibility complex (MHC) molecules: A mechanism for MHC-linked susceptibility to human autoimmune diseases. J Exp Med 1995; 181: 1597–1601.CrossRefGoogle Scholar
  24. 23.
    Wucherpfennig KW, Strominger JL. Selective binding of self peptides to disease-associated major histocompatibility complex (MHC) molecules: A mechanism for MHC-linked susceptibility to human autoimmune diseases. J Exp Med 1995; 181: 1597–1601.CrossRefGoogle Scholar
  25. 25.
    Conrad B, Weidmann E, Trucco G et al. Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology. Nature 1994; 371: 351–355.CrossRefGoogle Scholar
  26. 26.
    Khan MA. Pathogenesis of ankylosing spondylitis: recent advances. J Rheum 1993; 20: 1273–1277.Google Scholar
  27. 27.
    Richeldi L, Sorrentino R, Saltini C. HLA-DPB1 glutamate 69: A genetic marker of beryllium disease. Science 1993; 262: 242–244.CrossRefGoogle Scholar
  28. 28.
    DeGroot LJ, Quintans J. The causes of autoimmune thyroid disease. Endocr Rev 1989; 10: 537–562.CrossRefGoogle Scholar
  29. 29.
    Soliman M, Kaplan E, Yanagawa T et al. T cells recognize multiple epitopes in the human thyrotropin receptor extracellular domain. J Clin Endocr Metab 1995; 80: 905–914.CrossRefGoogle Scholar
  30. 30.
    Yanagawa T, Mangklabrucks A, DeGroot LJ. Strong association between HLA-DQA1*0501 and Grave’s disease in a male caucasian population. J Clin Endocrinol Metab 1994; 79: 227–229.CrossRefGoogle Scholar
  31. 31.
    Tamai H, Kimura A, Dong RP et al. Resistance to autoimmune thyroid disease is associated with HLA-DQ. J Clin Endocrinol Metab 1994; 78: 94–97.CrossRefGoogle Scholar
  32. 32.
    Tandon N, Zhang L, Weetman AP. HLA association with Hashimoto’s thyroiditis. Clin Endocrinol 1994; 34: 383–386.CrossRefGoogle Scholar
  33. 33.
    Farid NR. Immunogenetics of autoimmune thyroid disorders. Endocrinol Metab Clinic N Am 1987; 16: 229–245.Google Scholar
  34. 33.
    Farid NR. Immunogenetics of autoimmune thyroid disorders. Endocrinol Metab Clinic N Am 1987; 16: 229–245.Google Scholar
  35. 35.
    Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 1995; 80: 695–705.CrossRefGoogle Scholar
  36. 36.
    Lindstrom J. Autoimmune response to acetylcholine receptors in myasthenia gravis and its animal model. Adv Immunol 1979; 27: 1–50.CrossRefGoogle Scholar
  37. 37.
    Patrick J, Lindstrom J. Autoimmune response to acetylcholine receptor. Science 1973; 180: 871–872.CrossRefGoogle Scholar
  38. 38.
    Protti MP, Manfredi AA, Horton RM et al. Myasthenia gravis: recognition of a human autoantigen at the molecular level. Immunol Today 1993; 14: 363–368.CrossRefGoogle Scholar
  39. 39.
    Amagai M, Klaus-Kovtun V, Stanley JR. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell 1991; 67: 869–877.CrossRefGoogle Scholar
  40. 40.
    Shimoda S, Nakamura M, Ishibashi H et al. HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: Evidence of molecular mimicry in human autoimmune diseases. J Exp Med 1995; 181: 1835–1845.CrossRefGoogle Scholar
  41. 41.
    Gregersen P, Shen M, Song Q et al. Molecular diversity of HLA-DR4 haplotypes. Proc Natl Acad Sci USA 1986; 83: 2642–2646.CrossRefGoogle Scholar
  42. 42.
    Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis: an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 1987; 30: 1205–1213.CrossRefGoogle Scholar
  43. 43.
    Wicks I, McColl G, Harrison L. New perspectives on rheumatoid arthritis. Immunol Today 1994; 15: 553–556.CrossRefGoogle Scholar
  44. 44.
    Kallenberg CGM. Antitopoisomerase and anticentromere antibodies in the sclerodermatosus complex. Clin Rev Allergy 1994; 12: 221–235.Google Scholar
  45. 45.
    Oldstone MBA. Molecular mimicry and autoimmune disease. Cell 1987; 50: 810–820.CrossRefGoogle Scholar
  46. 46.
    Benjamin R, Parham P. Guilt by association: HLA-B27 and ankylosing spondylitis. Immunol Today 1990; 11: 137–142.CrossRefGoogle Scholar
  47. 47.
    Khan MA. An overview of clinical spectrum and heterogeneity of spondyloarthropies. Rheum Dis Clin North Am 1992; 18: 1–10.Google Scholar
  48. 48.
    López-Larrea C, Sujirachato K, Mehra NK et al. HLA-B27 subtypes in Asian patients with ankylosing spondylitis. Tissue Antigens 1995; 45: 169–176.CrossRefGoogle Scholar
  49. 49.
    Hill AVS, Allsopp CEM, Kwiatkowski D et al. HLA class I typing by PCR: HLA-B27 and an African B27 subtype. Lancet 1991; 337: 640–642.CrossRefGoogle Scholar
  50. 50.
    Madden DR, Gorga JC, Strominger JL et al. The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell 1992; 70: 1035–1048.CrossRefGoogle Scholar
  51. 51.
    Buxton SE, Benjamin RJ, Clayberger C et al. Anchoring pockets in human histocompatibility complex leukocyte antigen (HLA) class I molecules: analysis of the conserved B “45” pocket of HLA-B27. J Exp Med 1992; 175: 809–819.CrossRefGoogle Scholar
  52. 52.
    Breur-Vriesendorp BS, Vingerhoed J, Kuijpers KC et al. Effect of a Tyrto-His point mutation at position 59 in the alpha-1 helix of the HLA-B27 class-I molecule. on allospecific and virus-specific cytotoxic T-lymphocyte recognition. Scan J Rheumatology 1990; 87Suppl:S36–43.Google Scholar
  53. 53.
    Jardetzky TS, Lane WS, Robinson RA et al. Identification of self peptides bound to purified HLA-B27. Nature 1991; 353: 326–329.CrossRefGoogle Scholar
  54. 54.
    Carreno BM, Winter CC, Taurog JD et al. Residues in pockets B and F of HLA-B27 are critical in the presentation of an influenza A virus nucleoprotein peptide and influence the stability of peptide-MHC complexes. Int Immunol 1993; 5: 353–360.CrossRefGoogle Scholar
  55. 55.
    Rojo S, Garcia F, Villadangos JA et al. Changes in the repertoire of peptides bound to HLA-B27 subtypes and to site-specific mutants inside and outside pocket B. J Exp Med 1993; 177: 613–620.CrossRefGoogle Scholar
  56. 56.
    Colbert RA, Rowland-Jones SL, McMichael AJ et al. Allele-specific B pocket transplant in class I major histocompatibility complex protein changes requirement for anchor residue at P2 of peptide. Proc Natl Acad Sci USA 1993; 90: 6879–6883.CrossRefGoogle Scholar
  57. 57.
    Huet S, Nixon DF, Rothbard JB et al. Structural homologies between two HLA B27-restricted peptides suggest residues important for interacton with HLA B27. Int Immunol 1990; 2: 311–316.CrossRefGoogle Scholar
  58. 58.
    Rötzschke O, Falk K, Stevanovic S et al. Dominant aromatic/aliphatic C-terminal anchor in HLA-B*2702 and B*2705 peptide motifs. Immunogenetics 1994; 39: 74–77.CrossRefGoogle Scholar
  59. 59.
    Sidney J, del Guercio M-F, Southwood S et al. Several HLA alleles share overlapping peptide specificities. J Immunol 1995; 154: 247–259.Google Scholar
  60. 60.
    Fruci D, Rovero P, Butler RH et al. HLA class I binding of synthetic nonamer peptides carrying major anchor residue motifs of HLA-B27 (B*2705)-binding peptides. Immunogenetics 1993; 38: 41–46.CrossRefGoogle Scholar
  61. 61.
    Tanigaki N, Fruci D, Vigneti E et al. The peptide binding specificity of HLA-B27 subtypes. Immunogenetics 1994; 40: 192–198.CrossRefGoogle Scholar
  62. 62.
    Villadangos JA, Galocha B, López D et al. The role of binding pockets for amino-terminal peptide residues in HLA-B27 allorecognition. J Immunol 1992; 149: 505–510.Google Scholar
  63. 63.
    Falk K, Rötzschke O, Stevanovic S et al. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 1991; 351: 290–296.CrossRefGoogle Scholar
  64. 64.
    Brooks JM, Murray RJ, Thomas WA et al. Different HLA-B27 subtypes present the same immunodominant Epstein-Barr virus peptide. J Exp Med 1993; 178: 879–887.CrossRefGoogle Scholar
  65. 65.
    Hammer RE, Maika SD, Richardson JA et al. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human 132-m: an animal model of HLA-B27-associated human disorders. Cell 1990; 63: 1099–1112.CrossRefGoogle Scholar
  66. 66.
    Taurog JD, Maika SD, Simmons WA et al. Susceptibility to inflammatory disease in HLA-B27 transgenic rat lines correlates with the level of B27 expression. J Immunol 1993; 150: 4168–4178.Google Scholar
  67. 67.
    Taurog JD, Richardson JA, Croft JT et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 1994; 180: 2359–2364.CrossRefGoogle Scholar
  68. 68.
    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.CrossRefGoogle Scholar
  69. 69.
    Stern LJ, Brown JH, Jardetzky TS et al. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 1994; 368: 215–221.CrossRefGoogle Scholar
  70. 70.
    Jardetzky TS, Brown JH, Gorga JC et al. Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen. Nature 1994: 368: 711–718.CrossRefGoogle Scholar
  71. 71.
    Harris ED Jr. Etiology and pathogenesis of rheumatoid arthritis. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB, eds. Textbook of Rheumatology. Philadelphia: WB Saunders Co., 1993: 833–873.Google Scholar
  72. 72.
    Firestein G, Zvaifler N. The pathogenesis of rheumatoid arthritis. In: Pisetsky D, Snyderman R, eds. Immunology of Rheumatic Diseases. Philadelphia: WB Saunders, 1987: 447–461.Google Scholar
  73. 73.
    Stastny P. Mixed lymphocyte cultures in rheumatoid arthritis. J Clin Invest. 1976; 57: 1148–1157.CrossRefGoogle Scholar
  74. 74.
    Reinsmoen NL, Bach FH. Five HLA-D clusters associated with HLA-DR4. Hum Immunol 1982; 4: 249–258.CrossRefGoogle Scholar
  75. 75.
    Nepom BS, Nepom GT, Mickelson E et al. Electrophoretic analysis of human HLA-DR antigens from HLA-DR4 homozygous cell lines: Correlation between I3-chain diversity and HLA-D. Proc Natl Acad Sci 1983; 80: 6962–6966.CrossRefGoogle Scholar
  76. 76.
    Nepom GT, Nepom BS, Antonelli P et al. The HLA-DR4 family of haplotypes consists of a series of distinct DR and DS molecules. J Exp Med 1983; 159: 394–404.CrossRefGoogle Scholar
  77. 77.
    Seyfried CE, Gregersen P, Nepom BS et al. Functional polymorphisms among HLA-DR4’ DR beta chains associated with limited peptide diversity. Mol Immunol 1987; 24: 471–477.CrossRefGoogle Scholar
  78. 78.
    Deng H, Apple R, Clare-Salzler M et al. Determinant capture as a possible mechanism of protection afforded by major histocompatibility complex class II molecules in autoimmune disease. J Exp Med 1993; 178: 1675–1680.CrossRefGoogle Scholar
  79. 79.
    Hammer J, Bono E, Gallazzi F et al. Precise prediction of major histocompatibility complex class II-peptide interaction based on peptide side chain scanning. J Exp Med 1994; 180: 2353–2358.CrossRefGoogle Scholar
  80. 80.
    de Vries RRP. HLA and disease: from epidemiology to immunotherapy. Eur J Clin Invest 1992; 22: 1–8.CrossRefGoogle Scholar
  81. 81.
    Hastings RC, Gillis TP, Krahenbuhl JL et al. Leprosy. Clin Microbiol Reviews 1988; 1: 330–348.Google Scholar
  82. 82.
    Cohn ZA, Kaplan G. Hansen’s disease, cell-mediated immunity, and recombinant lymphokines. J Infect Dis 1991; 163: 1195–1200.CrossRefGoogle Scholar
  83. 83.
    van Eden W, de Vries RRP, Mehra NK et al. HLA segregation of tuberculoid leprosy: conformation of the DR2 marker. J Infect Dis 1980; 141: 693–701.CrossRefGoogle Scholar
  84. 84.
    Mehra NK. Role of HLA linked factors in governing susceptibility to leprosy and tuberculosis. Trop Med Parasitol 1990; 41: 352–354.Google Scholar
  85. 85.
    Todd JR, West BC, McDonald JC. Human leukocyte antigen and leprosy: study in northern Louisiana and review. Reviews Inf Dis 1990; 12: 63–74.CrossRefGoogle Scholar
  86. 86.
    van Eden W, de Vries RRP, D’Amaro J et al. HLA-DR associated genetic control of the type of leprosy in a population from Surinam. Hum Immunol 1982; 4: 343–350.CrossRefGoogle Scholar
  87. 87.
    van Eden W, Gonzales NM, de Vries RRP et al. HLA-Linked control of predisposition to lepromatous leprosy. J Infect Dis 1985; 151: 9–14.CrossRefGoogle Scholar
  88. 88.
    Rani R, Zaheer SA, Mukherjee R. Do human leukocyte antigens have a role to play in differential manifestations of multibacillary leprosy: a study on multibacillary leprosy patients from North India. Tissue Antigens 1992; 40: 124–127.CrossRefGoogle Scholar
  89. 89.
    Geluk A, van Meijgaarden KE, Janson AAM et al. Functional analysis of DR17(DR3)-restricted mycobacterial T cell epitopes reveals DR17-binding motif and enables the design of allele-specific competitor peptides. J Immunol 1992; 149: 2864–2871.Google Scholar
  90. 90.
    Malcherek G, Falk K, Rötzschke O et al. Natural peptides ligand motifs of two HLA molecules associated with myasthenia gravis. Int Immunol 1993; 5: 1229–1237.CrossRefGoogle Scholar
  91. 91.
    Rossman MD, Preuss O, Powers M., eds. Beryllium: Biomedical and Environmental Aspects. Baltimore: Williams and Wilkins, 1991.Google Scholar
  92. 92.
    Saltini C, Winestock K, Kirby M et al. Maintenance of alveolitis in patients with chronic beryllium disease by beryllium-specific helper T cells. N Engl J Med 1989; 320: 1103–1109.CrossRefGoogle Scholar
  93. 93.
    Eisenbud M, Lisson J. Epidemiological aspects of beryllium-induced non-malignant lung disease: a 30-year update. J Occup Med 1983; 25: 196–202.CrossRefGoogle Scholar
  94. 94.
    Saltini C, Kirby M, Trapnell BC et al. Biased accumulation of T lumphocytes with “memory”-type CD45 leukocyte common antigen gene expression on the epithelial surface of the human lung. J Exp Med 1990; 171: 1123–1140.CrossRefGoogle Scholar
  95. 95.
    Aronchick JM, Rossman MD, Miller WT. Chronic beryllium disease: diagnosis, radiographic findings, and correlation with pulmonary function tests. Radiology 1987; 163: 677–682.Google Scholar
  96. 95.
    Aronchick JM, Rossman MD, Miller WT. Chronic beryllium disease: diagnosis, radiographic findings, and correlation with pulmonary function tests. Radiology 1987; 163: 677–682.Google Scholar
  97. 97.
    Nerup J, Mandrup-Poulsen T, Helqvist S et al. On the pathogenesis of IDDM. Diabetologia 1994; 37 Suppl 2: S82–89.Google Scholar
  98. 98.
    Reimers JI, Bjerre U, Mandrup-Poulsen T et al. Interleukin lß induces diabetes and fever in normal rats by nitric oxide via induction of different nitric oxide synthases. Cytokine 1994; 6: 512–520.CrossRefGoogle Scholar
  99. 99.
    Ingle K. Calling all physicians for the diabetes prevention trial-type I. Diabetes Care 1994; 17: 1240–1241.Google Scholar
  100. 100.
    Akerbloom HK, Savilahti E, Saukkonen TT et al. The case for elimination of cow’s milk in early infancy in the prevention of type I diabetes: the Finnish experience. Diabetes Metab Rev 1993; 9: 269–278.CrossRefGoogle Scholar
  101. 101.
    Cheung R, Karjalainen J, VanderMeulen J et al. T cells from children with IDDM are sensitized to bovine serum albumin. Scan J Immunol 1994; 40: 623–628.CrossRefGoogle Scholar
  102. 102.
    Stiller CR, Dupré J, Gent M et al. Effects of cyclosporine immunosuppression in insulin-dependent diabetes mellitus of recent onset. Science 1984; 223: 1362–1367.CrossRefGoogle Scholar
  103. 103.
    Todd JA, Bell JL, McDevitt HO. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 1987; 329: 559–604.CrossRefGoogle Scholar
  104. 104.
    Khalil I, d’Auriol L, Gobet M et al. A combination of HLA-DQ13 Asp57negative and HLA-DQa Arg52 confers susceptibility to insulin-dependent diabetes mellitus. J Clin Invest 1990; 85: 1315–1319.CrossRefGoogle Scholar
  105. 105.
    Brown JH, Jardetzky T, Saper MA et al. A hypothetical model of the foreign antigen binding site of Class II histocompatibility molecules. Nature 1988; 332: 845–850.CrossRefGoogle Scholar
  106. 106.
    Davis M. Serial engagement proposed. Nature 1995; 375: 104.CrossRefGoogle Scholar
  107. 107.
    Johansen BH, Buus S, Vartdal F et al. Binding of peptides to HLA-DQ molecules: peptide binding properties of the disease-associated HLADQ(al*0501, 131*0201) molecule. Int Immunol 1994; 6: 453–461.CrossRefGoogle Scholar
  108. 108.
    Chicz RM, Lane WS, Robinson RA et al. Self-peptides bound to the type I diabetes associated class II MHC molecules HLA-DQ1 and HLA-DQ8. Int Immunol 1994; 6: 1639–1649.CrossRefGoogle Scholar
  109. 109.
    Chicz RM, Urban RG, Gorga JC et al. Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles. J Exp Med 1993; 178: 27–47.CrossRefGoogle Scholar
  110. 110.
    Santamaria P, Boyce-Jacino MT, Lindstrom AL et al. Detection of novel sequence heterogeneity and haplotype diversity of HLA class II genes. Immunogenetics 1991; 33: 374–387.CrossRefGoogle Scholar
  111. 111.
    Kim J, Urban RG, Strominger JL et al. Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1. Science 1994; 266: 1870–1874.CrossRefGoogle Scholar
  112. 112.
    Gale EAM, Bingley PJ. Can we prevent IDDM? Diabetes Care 1994; 17: 339–344.Google Scholar
  113. 113.
    Karin N, Mitchell DJ, Brocke S et al. Reversal of experimental autoimmune encephalomyelitis by a soluble peptide variant of a myelin basic protein epitope: T cell receptor antagonism and reduction of interferon y and tumor necrosis factor a production. J Exp Med 1994; 180: 2227–2237.CrossRefGoogle Scholar
  114. 114.
    Fu XT, Bono CP, Woulfe SL et al. Pocket 4 of the HLA-DR (a411*0401) molecule is a major determinant of T cell recognition of peptide. J Exp Med 1995; 181: 915–926.CrossRefGoogle Scholar
  115. 115.
    Sette A, Adorini L, Colon SM et al. Capacity of intact proteins to bind to MHC class II molecules. J Immunol 1989; 143: 1265–1267.Google Scholar
  116. 116.
    Lee P, Matsueda GR, Allen PM. T cell recognition of fibrinogen: a determinant on the Au-chain does not require processing. J Immunol 1988; 140: 1063–1068.Google Scholar

Copyright information

© R.G. Landes Company 1996

Authors and Affiliations

  • Joan C. Gorga
  • Dimitri Monos

There are no affiliations available

Personalised recommendations