Advertisement

The Molecular Basis of HLA—Disease Association

  • J. I. Bell
  • J. A. Todd
  • H. O. McDevitt
Part of the Advances in Human Genetics book series (AHUG, volume 18)

Abstract

The human major histocompatibility complex (MHC) has been the object of more extensive characterization than any other polymorphic system in man. This complex of loci, situated on the short arm of chromosome 6, has particularly attracted the attention of those interested in the genetic control of immune responsiveness, as these loci are essential components of most humoral and cellular responses. The observation that these loci, which had been defined as several polymorphic series by serology, represented some of the immune response (Ir) genes that had been described in the mouse by McDevitt and Tyan (1968) stimulated further effort to characterize these genes and their products fully and to define further their biological role in the immune response. A further impetus to this work came from the observation that certain MHC alleles were strongly associated with susceptibility to over 40 diseases, mostly autoimmune in nature (Stastny et al., 1983).

Keywords

Rheumatoid Arthritis Major Histocompatibility Complex Celiac Disease Disease Susceptibility Major Histocompatibility Complex Molecule 
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. Acha Orbea, H., and McDevitt, H. O., 1987, The AR chain in the NOD mouse is unique. Proc. Natl. Acad. Sci. U.S.A. 84:2435–2439.CrossRefGoogle Scholar
  2. Ajitkumar, P., Geier, S., Kesari, K. V., Borriello, F. Nakagawa, M., Bluestone, J. A., Saper, M. M., Wiley, D. C., and Nathenson, S. G.. 1988, Evidence that multiple residues on both the a-helices of the class I MHC molecule are simultaneously recognized by the T cell receptor, Cell 54:47–56.PubMedCrossRefGoogle Scholar
  3. Allen, P. M., Matsueda, G. R., Evans, R. J., Dunbar, J. B., Marshall, G. R., and Unanue, E. R., 1987, Identification of the T-cell and Ia contact residues of a T-cell antigenic epitope, Nature 327:713–716.PubMedCrossRefGoogle Scholar
  4. Auffray, C., Lille, J. W., Arnot, D., Grossberger, D., Kappes, D., and Strominger J. L., 1984, Isotope and allotypic variation of human class II histocompatibility antigen a chain genes, Nature 308:327–333.PubMedCrossRefGoogle Scholar
  5. Bach, F. H., Ohta, N., Anichini, A., and Reinsmoen N. L., 1986, Cellular detection of HLA class II-encoded determinants: Subtype polymorphisms of HLA-D, in: HLA Class 11 Antigens (B. G. Solheim, E. Moller, and S. Ferrone, eds.), Springer, Berlin. pp. 249–265.Google Scholar
  6. Batchelor, J. R., and Morris, P. J., 1978, Juvenile onset diabetes, in: Histocompatibility Testing 1977 (J. Bodmer, J. R. Batchelor, W. Bodmer, H. Festenstein, and P. J. Morris, eds.), Munksgaard, Copenhagen, pp. 211–213.Google Scholar
  7. Bell, J. I., Denney, D. W., and McDevitt, H. O., 1985, Structure and polymorphism of murine and human class II major histocompatibility antigens, lmmunal. Rev,84:51–71.CrossRefGoogle Scholar
  8. Bell, J. I., Smoot, S., Newby, C., Toyka, K., Rassenti, L., Smith, K., Hohfeld, R., McDevitt, H. O., and Steinman, L., 1986, DQ beta chain polymorphism linked to myasthenia gravis, Lancet 1:1058–1060.PubMedCrossRefGoogle Scholar
  9. Bell, J. I., Denney, D., MacMurray, A., Foster, L., Watling, D., and McDevitt, H. O., 1987a, Molecular mapping of class II polymorphisms in the human major histocompatibility complex I DRß, J. immunol. 139:562–573.Google Scholar
  10. Bell, J. I., Denney, D. W., Foster, L., Belt, T., Todd, J. A., and McDevitt, H. O., 1987b, Allelic polymorphism in the HLA-DR subregion, Proc. Natl. Acad. Sci. U.S.A. 84:6234–6238.CrossRefGoogle Scholar
  11. Benacerraf, B., and McDevitt, H. O., 1972, Histocompatibility-linked immune response genes, Science 175:273–279.PubMedCrossRefGoogle Scholar
  12. Berte, C. C., Tanigaki, N., Tosi, R., Gorski, J., and Mach, B., 1988, Serological recognition of HLA-DR allodeterminant corresponding to DNA sequence involved in gene conversion, Bnmunogenetics 27:167–173.CrossRefGoogle Scholar
  13. Betuel, H., Gebuhrer, L., Descos, L., Bertrand, J., Freycon, F., and Lepetit, J. C.. 1980, Celiac disease and its association with HLA markers, in: Histocompatibility Testing 1980 (P. Teraski, ed.), UCLA Tissue Typing Laboratory, Los Angeles, pp. 668–672.Google Scholar
  14. Bjorkman, P. J., Saper, M. A., Samraoui, B., Bennett, W. S., Strominger, J. L., and Wiley, D. C., 1987a, Structure of the human class I histocompatibility antigen, HLA-A2, Nature 329:506–511.CrossRefGoogle Scholar
  15. Bjorkman, P. J., Saper, M. A., Samraoui, B., Bennett, W. S., Strominger, J. L.. and Wiley, D. C., 1987b, The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens, Nature 329:512–516.CrossRefGoogle Scholar
  16. Bodmer, J. G., Kennedy, L. J., Lindsa, J., and Wasik, A. M., 1987a, Application of serology and the ethnic distribution of three locus HLA haplotypes, Br. Med. Bull. 43:94–121.Google Scholar
  17. Bodmer, J., Bodmer W., Heyes, J., So, A., Tanks, S., Trowsdale, J., and Young, J., 1987b, Identification of HLA-DP polymorphism with DPa, and DP0 probes and monoclonal antibodies: Correlation with primed lymphocyte typing, Proc. Natl. Acad. Sci. U.S.A. 84:4596–4600.CrossRefGoogle Scholar
  18. Bottazzo, G. F., Pujol-Borrell, R., Hanafusa, T., and Feldmann, M., 1983. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity, Lancet 2:1115–1118.PubMedCrossRefGoogle Scholar
  19. Brautbar, C., Moscovitz, M., Livshits, T., Haim, S., Hacham-Zadeh, S., Cohen, C. A., Sharon, R., and Nelken, D., 1980, HLA-DRw4 in pemphigus vulgaris patients in Israel, Tissue Antigens 16:238–243.PubMedCrossRefGoogle Scholar
  20. Brewerton, D. A., Caffrey, M., Hart, F. D., James, D. C. O., Nicholls, A., and Sturrock, R. D., 1973, Ankylosing spondylitis and HLA-B 27, Lancet 1:904–907.PubMedCrossRefGoogle Scholar
  21. Brown, J. H., Jardetzky, T., Saper, M. A., Samraoui, B., Bjorkman, P. J., and Wiley, D. C., 1988, A hypothetical model of the foreign antigen binding site of class II histocompatibility antigens, Nature 332:845–850.PubMedCrossRefGoogle Scholar
  22. Bugawan, T. L., Horn, G. T., Long, C. M., Mickelson, E., Hansen, J. A., Ferrara, G. B., Angelini, G., and Erlich, H. A., 1988, Analysis of HLA-DP allelic sequence polymorphism using the in vitro enzymatic DNA amplification of DP-a and DP-f3 loci, J. Immunol. 141:4024–4030.PubMedGoogle Scholar
  23. Campbell, R. D., 1987, The molecular genetics and polymorphism of C2 and factor B, Br. Med. Bull. 43:37–49.PubMedGoogle Scholar
  24. Carroll, M. C., Campbell, R. D., Bentley, D. R., and Porter, R. R., 1984, A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature 307:237–241.PubMedCrossRefGoogle Scholar
  25. Christiansen, F. T., Kelly, H., and Dawkins, R. L., 1984, Rheumatoid arthritis, in: Histocompatibility Testing 1984 (E. D. Albert, M. P. Baur, and W. R. Mayr, eds.), Springer, Berlin, pp. 378–383.Google Scholar
  26. Clerget-Darpoux, F., Govaerts, A., and Feingold, N., 1984, HLA and susceptibility to multiple sclerosis, Tissue Antigens 23:240–245.Google Scholar
  27. Cohen, D., LeGall, I., Marcadet, A., Font, M. P., Lalouel, J. M., and Dausset, J., 1984, Clusters of HLA class II ß restriction fragments describe allelic series, Proc. Natl. Acad. Sci. U.S.A. 81:7870–7874.PubMedCrossRefGoogle Scholar
  28. Coppin, H. L., and McDevitt, H. 0., 1986, Absence of polymorphism between HLA-B27 genomic exon sequences isolated from normal donors and ankylosing spondylitis patients, J. Iminunol. 137:2168–2172.Google Scholar
  29. Cresswell, P., Turner, M. J., and Strominger, J. L., 1973, Papain-solubilized HL-A antigens from cultured human lymphocytes contain two peptide fragments, Proc. Nail. Acad. Sci. U.S.A. 70:1603–1607.CrossRefGoogle Scholar
  30. Crumpton, M. J., Bodmer, J. G., Bodmer, W. F., Heyes, J. M., Lindsay, J., and Rudd, C. E.. 1984. Biochemistry of class H antigens: Workshop report, in: Histocompatibility Testing-1984 (E. D. Albert and W. Mayr, eds.), Springer, Berlin, pp. 29–37.Google Scholar
  31. Dawkins, R. L., 1980, Myasthenia gravis, in: Histoconapafibility Testing 1980 (P. Teraski, ed.), UCLA Tissue Typing Laboratory, Los Angeles, pp. 662–667.Google Scholar
  32. Dunham, I., Sargent, C. A., Trowsdale, J., and Duncan Campbell, R., 1987, Molecular map of the human major histocompatibility complex by pulsed-field gel electrophoresis, Proc. Natl. Acad. Sci. U.S.A. 84:7237–7241.PubMedCrossRefGoogle Scholar
  33. Duquesnoy, R. J., Marrari, M., Hackbarth, S., and Zeevi, A., 1984, Serological and cellular definition of a new HLA-DR associated determinant, MCI, and its association with rheumatoid arthritis, Hum. Immunol. 10:165–176.PubMedCrossRefGoogle Scholar
  34. Ebers, G. C., Paty, D. W., Stiller, C. R., Nelson, R. F., Seland, T. P., and Larsen, B., 1982, HLA-typing in multiple sclerosis sibling pairs, Lancet - 2:88–90..PubMedCrossRefGoogle Scholar
  35. Ebers, G. C., Bulman, D. E., Sadovnick, A. D., Paty, D. W., Warren, S., Hader, W., Murray, J., Seland, P., Duquette, P., Grey, T., Nelson, R., Nicolle, M., and Brunet, D., 1986, A population-based study of multiple sclerosis in twins, N. Engl. J. Med. 315:1638–1642.PubMedCrossRefGoogle Scholar
  36. Eckels, D. D., Lake, P., Lamb, J. R., Johnson, A. H., Shaw, S., Woody, J. N., and Hartzman, R. J., 1983, SB-restricted presentation of influenza and herpes simplex virus antigens to human T lymphocyte clones, Nature 301:716–718.PubMedCrossRefGoogle Scholar
  37. Erlich, H., Steiler, D., and Grumet, C., 1983, Restriction fragment length polymorphism analysis of HLA-typed families using cloned HLA probes, in: Banbury Report 14; Recombinant DNA Applications to Human Diseases, Cold Spring Harbor Laboratory, New York, pp. 327–334.Google Scholar
  38. Festenstein, H., and Oilier, B., 1987, Cellular typing and functional heterogeneity of MHCencoded products, Br. Med. Bull. 43:122–155.PubMedGoogle Scholar
  39. Geczy, A. F., McGuigan, L. E., Sullivan, J. S., and Edmonds, J. P.. 1986, Cytotoxic T lymphocytes against disease associated determinant(s) in anklyosing spondylitis, J. Exp. Med. 164:932–937.PubMedCrossRefGoogle Scholar
  40. Germain, R. N., and Quill, H., 1986, Unexpected expression of a unique mixed-isotope class II MHC molecule by transfected L cells, Nature 320:72–75.PubMedCrossRefGoogle Scholar
  41. Goronzy, J., Weyand, C. M., and Fathman, C. G., 1986, Shared T cell recognition sites on HLA class II molecules of patients with seropositive rheumatoid arthritis, J. Clin. Invest. 77:1042–1049.PubMedCrossRefGoogle Scholar
  42. Gorski, J., and Mach, B., 1986, Polymorphism of human la antigen: Gene conversion between two DRß loci results in a new HLA-DIDR specificity, Nature 322:67–70.PubMedCrossRefGoogle Scholar
  43. Gotch, F. M., Rothbard, J., Howland, K., Townsend, A., and McMichael, A. J., 1987. Cytotoxic T lymphocytes recognize a fragment of influenza virus matrix protein in association with HLA-A2, Nature 326:881–882.PubMedCrossRefGoogle Scholar
  44. Gregersen, P. K., Shen, M., Song, Q. L., Merryman, P., Degar, S., Seki, T., Maccari, J., Goldberg, D., Murphy, H., Schwenger, J., Want, C. Y., Winchester, R. J., Nepom, G T., and Silver, J., 1986, Molecular diversity of HLA-DR4 haplotypes, Proc. Natl. Acad. Sci. U.S.A. 83:2642–2646.PubMedCrossRefGoogle Scholar
  45. Guillet, J. G., Lai, M. Z., Binner, T. J., Smith, J. A., and Gefner, M. L., 1986, Interaction of peptide antigens and class II major histocompatibility complex antigens. Nature 324:260–262.PubMedCrossRefGoogle Scholar
  46. Hardy, D. A., Bell, J. I., Long, E. O., Lindsten, T., and McDevitt, H. O., 1986, Mapping of the class II region of the human major histocompatibility complex by pulsed-field gel electrophoresis, Nature 323:453–455.PubMedCrossRefGoogle Scholar
  47. Horn, G. T., Bugawan, T. L., Long, C. M., and Erlich, H. A., 1988, HLA class II antigens and susceptibility to insulin-dependent diabetes mellitus, Proc. Natl. Acad. Sri. U.S.A. 85:6012–6016.CrossRefGoogle Scholar
  48. Hors, J., and Dausset, J., 1983, HLA and susceptibility to Hodgkin’s disease, Immunol. Rev. 73:167–192.CrossRefGoogle Scholar
  49. Hughes, G. R. V., and Batchelor, J. R., 1983, Genetics of systemic lupus erythematosus, Br. Med. J. 1:416–417.CrossRefGoogle Scholar
  50. Ishikawa, I., Kojima, H., Nakayama, T., Junikane, H., Hawkin, S., Fukasawa, Y., Ikeda, H., Ogasawara, K., Kasahara, M., Tajima, Y., Kakuta, Y., Wakisaka, A., and Aizawa, M., 1987, Detection of a novel HLA-DQ specificity: Serological and immunochemical analyses by a monoclonal antibody, Immunogenetics 26:143–149.PubMedCrossRefGoogle Scholar
  51. Jacob, C. O., and McDevitt, H. O., 1988, Tumor necrosis factor a in murine autoimmune “lupus” nephritis, Nature 331:356–358.PubMedCrossRefGoogle Scholar
  52. Johnston, C., Pyke, D. A., Cudworth, A. G., and Wolf, E., 1983,. HLA-DR typing in identical twins with insulin-dependent diabetes mellitus: A difference between concordant and discordant pairs, Br. Med. J. 286:253–255.CrossRefGoogle Scholar
  53. Kappes, D. J., Arnot, D., Okada, K., and Strominger, J. L., 1984, Structure and polymorphism of the HLA class II SB light chain genes, EMBO J. 3:2985–2993.PubMedGoogle Scholar
  54. Kaufman, J. F., Auffray, C., Korman, J. K., Shackelford, D. A.. and Strominger, J., 1984, The class II molecules of the human and muriné major histocompatibility complex, Cell 36:1–13.PubMedCrossRefGoogle Scholar
  55. Kim, S. J., Holbeck, S. L., Nisperos, B., Hansen, J. A., Maeda, H., and Nepom, G. T., 1985, Identification of a polymorphic variant associated with HLA-DQw3 and characterized by specific restriction sites within the DQ0-chain genes, Proc. Natl. Acad. Sci. U.S.A. 82:8139–8143.PubMedCrossRefGoogle Scholar
  56. Lee, B. S. M., Rust, N. A., McMichael, A. J., and McDevitt, H. O., 1987, HLA-DR2 subtypes form an additional supertypic family of DR0 alleles, Proc. Natd. Acad. Sci. U.S.A. 84:4591–4595.CrossRefGoogle Scholar
  57. Lotteau, V., Teyton, L., Burroughs, D., and Charron, D., 1987, A novel HLA class II molecule (DR„ — DQp) created by mismatched isotype pairing, Nature 329:339–341.PubMedCrossRefGoogle Scholar
  58. MacMurray, A. J., Bell, J. I., Denney, D., Watling, D., Foster, L. S., and McDevitt, H. O., 1987, Molecular mapping class II polymorphisms in the human major histocompatibility complex. II. DQß, J. Immunol. 139:574–586.PubMedGoogle Scholar
  59. Matsuki, K., Juji, T., and Satake, M., 1987, A novel HLA class II alloantigen detected by an alloantiserum TK2, Hum. Immunol. 18:247–256.PubMedCrossRefGoogle Scholar
  60. McDevitt, H. O., and Tyan, M. L., 1968, Genetic control of the antibody response in inbred mice: Transfer of response by spleen cells and linkage to the major histocompatibility (H-2) locus, J. Exp. Med. 128:1–11.PubMedCrossRefGoogle Scholar
  61. McIntyre, K., and Seidmann, J.. 1984, Nucleotide sequence of mutant I-Ar’2 gene is evidence for genetic exchange between mouse immune response genes, Nature 308:551–553.PubMedCrossRefGoogle Scholar
  62. Monos, D. S., Spielman, R. S., Gogolin, K. J., Radka, S. F., Baker, L., Zmijeswki, C. M., and Kamoun, M., 1987, HLA-DQw3.2 allele of the DR4 haplotype is associated with insulin-dependent diabetes: Correlation between DQ0 restriction fragments and DQ0 chain variation, Immunogenetics 26:299–303.PubMedCrossRefGoogle Scholar
  63. Morel, P. A., Dorman, J. S., Todd, J. A., McDevitt, H.O., and Trucco, M., 1988, Aspartic acid at position 57 of the DQß chain protects against Type 1 diabetes: A famility study, Proc. Natl. Acad. Sci. U.S.A. 85:8111–8115.PubMedCrossRefGoogle Scholar
  64. Nepom, B. S., Nepom, G. T., Mickelson, E., Schaller, J. G., Antonelli, P., and Hansen, J. A., 1984, Specific HLA-DR4-associated histocompatibility molecules characterize patients with seropositive juvenile rheumatoid arthritis, J. Clin. invest. 74:287–291.PubMedCrossRefGoogle Scholar
  65. Nepom, G. T., Hansen, J. A., and Nepom, B. S., 1987. The molecular basis for class II associations with rheumatoid arthritis, J. Clin. Immunol. 7:1–7.PubMedCrossRefGoogle Scholar
  66. Nishimoto, H., Kikutani, H., Yamamura, K.-I., Kishimoto, T., 1987, Prevention of autoimmune insulitis by expression of 1-E molecules in NOD mice, Nature 328:432–434.PubMedCrossRefGoogle Scholar
  67. Okada, K., Boss, M. J., Prentice, H., Spies, T., Mengler, R., Auffray, C., Lillie, J., Grossberger, D., and Strominger, J. L., 1985, Gene organization of DC and DX subregions of the human major hsitocompatibility complex, Proc. Natl. Acad. Sci. 82:3410–3414.PubMedCrossRefGoogle Scholar
  68. Owerbach, D., Lernmark, A., Platz, P., Ryder, L. P., Rask, L., Peterson, P. A., and Ludvigsson, J., 1983, HLA-D region p chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulin-dependent diabetic individuals, Nature 303:815–817.PubMedCrossRefGoogle Scholar
  69. Parham, P., Lorien, C. E., Lawlor, D. A., Ways, J. P., Holmes, N., Coppin, H. L., Salter, R. D., Wan, A. M., and Ennis, P. D., 1988, The nature of polymorphism in HLA-A, B, C molecules, Proc. Natl. Acad. Sci. U.S.A. 85:4005–4009.PubMedCrossRefGoogle Scholar
  70. Parham, P., Lomen, C. E., Lawlor, J. A., Ways, J. P., Holmes, N., Coppin, H. L., Salter, R. D., Wan, A. M., Ennis, P. D., 1988, Nature of polymorphism in HLA-A-B-C molecules, Proc. Natl. Acad. Sci. U.S.A. 85:4005–4009.PubMedCrossRefGoogle Scholar
  71. Porter, R. R., 1983, Complement polymorphism, the major histocompatibility complex and associated diseases: A speculation, Mol. Biol. Med. 1:161–168.PubMedGoogle Scholar
  72. Prochaska, M., Leiter, E. H., Serreze, D. V., and Coleman, D. L., 1987, Three recessive loci required for insulin-dependent diabetes mellitus in nonobese diabetic mice, Science 237:286–288.CrossRefGoogle Scholar
  73. Rojo, S., Aparicio, P., Choo, S. Y., Hansen, J. A., and Lopez de Castro, J., 1987, Structural analysis of HLA-B27 population variant, B27f: Multiple patterns of amino acid changes within a single polypeptide segment generate polymorphism in HLA-B27, J. Immunol. 139:831–836.PubMedGoogle Scholar
  74. Rossini, A. A., Mordes, J. P., and Like, A. A., 1985, Immunology of insulin-dependent diabetes mellitus, Annu. Rev. Immunol. 3:289–320.PubMedCrossRefGoogle Scholar
  75. Rotter, J. I., and Landlaw, E. M., 1984, Measuring the genetic contribution of a single locus to a multilocus disease, Clin. Genel. 26:529–542.CrossRefGoogle Scholar
  76. Saiki, R. K., Bugawan, T. L., Horn, G. T., Mullis, K. B., and Erlich, H. A., 1986. Analysis of enzymatically amplified)3-globulin and HLA-DQ„ DNA with allele-specific oligonucleotide probes, Nature 324:163–166.PubMedCrossRefGoogle Scholar
  77. Sasazuki, T., Nishimura, Y., Muto, M., and Ohta, N., 1983, HLA linked genes controlling immune response and disease susceptibility, Immunol. Rev. 70:51–78.PubMedCrossRefGoogle Scholar
  78. Schreuder, G. M. T., and Van Leeuwen, A., 1986, Alloantisera against human class II antigens: Definition and methodology, in: IILA Class II Antigens (B. G. Solheem, E. Moller, and S. Ferrone, eds.), Springer. Berlin, pp. 187–203.Google Scholar
  79. Schreuder, G. M. T., Tilanus, M. G. J., Bontrop, R. E., Bruining, G. J., Giphart, M. J., Van Rood, J. J., and DeVries, R. R. P., 1986, HLA-DO polymorphism associated with resistance to type I diabetes detected with monoclonal antibodies, isoelectric point differences and restriction fragment length polymorphism, J. Exp. Med. 164:938–943.PubMedCrossRefGoogle Scholar
  80. Serjeantson, S. W., 1983, HLA and susceptibility to leprosy, Immunol. Rev. 70:89–112.PubMedCrossRefGoogle Scholar
  81. Servenius, B., Gustafsson, K., Widmark, E., Emmoth, E., Andersson, G., Larhammar, D., Rask, L., and Peterson, P. A., 1984, Molecular map of the human HLA-SB (HLADP) region and sequence of an SI3„ (DP„) pseudogene, EMBO J. 3:3209–3214.PubMedGoogle Scholar
  82. Sette, A., Buus, S., Colon, S., Smith, J. A., Miles, C., and Grey, H. M., 1987, Structural characteristics of an antigen required for its interaction with la and recognition by T cells, Nature 328:395–399.PubMedCrossRefGoogle Scholar
  83. Seyfried, C. E., Mickelson, E., Hansen, J. A., and Nepom, G. T., 1988, A specific nucleotide sequence defines a functional T cell recognition epitope shared by diverse HLA-DR specificities, Hum. Immunol. (in press).Google Scholar
  84. Shaw, S., Kavathas, P., Pollack, M. S., Charmot, D., and Mawas, C., 1981, Family studies define a new histocompatibility locus, SB, between HLA-DR and GLU, Nature 293:745–747.PubMedCrossRefGoogle Scholar
  85. Singer, K. H., Hashimoto, K., Jensen, P. J., Morioka, S., and Lazarus, G. S., 1985, Pathogenesis of autoimmunity in pemphigus, Anna. Rev. Immunol. 3:87–108.CrossRefGoogle Scholar
  86. Sinha, A. A., Brautbar, C., Szafer, F., Friedmann, A., Tzfoni, E., Todd, J. A., Steinman, L., and McDevitt, H. O., 1987, A newly characterized HLA DQs allele associated with pemphigus vulgaris, Science 239:1026–1029.CrossRefGoogle Scholar
  87. Spielman, R. S., Lee, J., Bodmer, W. F., Bodmer, J. G., and Trowsdale, J.. 1984, Six HLA-D region a chain genes on human chromosome 6: Polymorphism and associations of DC,,-related sequences with DR types, Proc. Nall. Acad. Sci. U.S.A. 81:3461–3465.CrossRefGoogle Scholar
  88. Spies, T., Sorrentino, R., Boss, J. M., Okada, K., and Strominger, J. L., 1985, Structural organization of the DR subregion of the human major histocompatibility complex, Proc. Natl. Acad. Sci. U.S.A. 82:5165–5169.PubMedCrossRefGoogle Scholar
  89. Stastny, P., 1978, Association of the B-cell alloantigen DRw4 with rheumatoid arthritis, N. Engl. J. Med. 298:869–871.PubMedCrossRefGoogle Scholar
  90. Stastny, P., Ball, E. J., Dry, P. J., and Nunez, G., 1983, The human immune response region (HLA-D) and disease susceptibility, Immunol. Rev. 70:111–154.CrossRefGoogle Scholar
  91. Steinmetz, M., 1986, Structural and functional studies of mouse class II genes, in: HLA Class II Antigens (B. G. Sohheem, E. Moller, and S. Ferrone, eds.), Springer, Berlin, pp. 109–127.Google Scholar
  92. Svejgaard, A., Platz, P., and Ryer, L. P., 1980, Insulin-dependent diabetes mellitus, in: Histocompatibility Testing 1980 (P. Teraski, ed.), UCLA Tissue Typing Laboratory, Los Angeles, pp. 638–642.Google Scholar
  93. Szafer, F., Brautbar, C., Tzfoni, E., Frankel, G., Sherman, L., Cohen, I., Hacham-Zadeh, S., Aberer, W., Tappeiner, G., Holubar, K., Steinman, L., and Friedmann, A., 1987, Detection of disease-specific restriction fragment length polymorphisms in pemphigus vulgaris linked to the DQwI and DQw3 alleles of the HLA-D region, Proc. Natl. Acad. Sci. U.S.A. 84:6542–6545.PubMedCrossRefGoogle Scholar
  94. Teisberg, P., Olaisen, B., Nordhagen, R., Thorsby, E., and Gedde-Dahl, T., 1980, A haemolytically non-active C4 gene product, Immunobiology 158:91–95.PubMedGoogle Scholar
  95. Tiwari, J. L., and Teraski, P. I. (eds.), 1985, HLA and Disease Association, Springer, New York.Google Scholar
  96. Todd, J. A., Bell, J. I., and McDevitt, H. O., 1987, HLA-DQ0 gene contributes to suscep- tibility and resistance to insulin-dependent diabetes mellitus, Nature 329:599–604.PubMedCrossRefGoogle Scholar
  97. Todd, J. A., Acha-Orbea, H., Bell, J. I., Chao, N., Fronek, Z., Jacob, C. O., McDermott, M., Sinha, A. A., Timmerman, L., Steinman, L., and McDevitt, H. O., 1988a, A molecular basis for MHC class II-associated autoimmunity, Science 240:1003–1009.CrossRefGoogle Scholar
  98. Todd, J. A., Bell, J. I., and McDevitt, H. O., 1988b, A molecular basis for genetic susceptibility to insulin-dependent diabetes mellitus, Trends Genet. 4:129–134.CrossRefGoogle Scholar
  99. Tonnelle, C., DeMars, R., and Long, E. O., 1985, DO0: A new f3 chain gene in HLA-D with a distinct regulation of expression, EMBO J. 4:2839–2847.PubMedGoogle Scholar
  100. Townsend, A. R. M., McMichael, A. J., Carter, N. P., Huddleston, J. A., and Brownlee, G. G., 1984, Cytotoxic T cell recognition of the influenza nucleoprotein and haemagglutinin expressed in transfected mouse L cells, Cell 39:13–25.PubMedCrossRefGoogle Scholar
  101. Townsend, A. R. M., Rothbard, J., Gotch, F. M., Bahadur, G., Wraith, D., and McMichael, A. J., 1986, The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides, Cell 44:959–968.PubMedCrossRefGoogle Scholar
  102. Trowsdale, J.., and Campbell, R. C., 1988. Physical map of the human HLA region, Immuual. Today 9:34–35.CrossRefGoogle Scholar
  103. Trowsdale, J., and Kelly, A., 1985, The human HLA class II a chain gene DZ., is distinct from genes in the DP, DQ and DR subregions, EMBU T. 4:2231–2237.Google Scholar
  104. Trowsdale, J., Kelly, A., Lee, J., Carson, S., Austin, P., and Travers, P., 1984, Linkage map of two HLA-SB ß and HLA SB a-related genes: An intron in one of the SBA genes contains processed pseudogene, Cell 38:241–249.PubMedCrossRefGoogle Scholar
  105. Trowsdale, J., Young, J. A. T., Kelly, A. P., Austin, P. J., Carson, S., Meunier, H., So, A., Erlich, H. A., Spielman, R. S., Bodmer, J., and Bodmer, W. F., 1985, Structure, sequence and polymorphism in the HLA-D region, Immunol. Rev. 85:5–43.PubMedCrossRefGoogle Scholar
  106. Weiss, E. H., Mellor, A., Golden, L., Fahrner, K., Simpson, L, Hurst, J., and Flavell, R. A., 1983, The structure of a mutant H-2 gene suggests that the generation of polymorphism in H-2 genes may occur by gene-conversion-like events, Nature 301:671–674.PubMedCrossRefGoogle Scholar
  107. Wordsworth, P., and Bell, J. I., Third allelic hypervariable region of DRß contributes to susceptibility to rheumatoid arthritis (submitted).Google Scholar
  108. Wu, S., Saunders, T. L., and Bach, F. H., 1986. Polymorphism of human la antigens generated by reciprocal intergenic exchange between two DR0 loci, Nature 324:676–679.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • J. I. Bell
    • 1
  • J. A. Todd
    • 2
  • H. O. McDevitt
    • 3
  1. 1.Nuffield Department of Clinical MedicineUniversity of Oxford John Radcliffe HospitalHeadington, OxfordUK
  2. 2.Nuffield Departments of Clinical Medicine and SurgeryUniversity of Oxford John Radcliffe HospitalHeadington, OxfordUK
  3. 3.Department of Microbiology and ImmunologyStanford University School of MedicineStanfordUSA

Personalised recommendations