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. 1988 Jun;72(3):362–366.

Novel HLA class II-associated structural patterns in coeliac disease and type I diabetes.

N Fernandez 1, G A Hitman 1, H Festenstein 1, L Garde 1, M Labeta 1, J A Walker-Smith 1, J A Sachs 1
PMCID: PMC1541555  PMID: 2901925

Abstract

Cell membrane antigens were precipitated from EBV transformed cell lines by a monomorphic DR monoclonal antibody. Three mutually exclusive patterns with two glycoproteins (g25 and g28) that had not been previously identified, were observed. The first, g25+/g28- was found in all cell lines from 40 healthy individuals; a second, g25-/g28- was found in 4/7 coeliac and 2/4 IDDM patients and a third, g25+/g28+ was found in 3/7 coeliac and 1/4 IDDM patients. RFLP analysis with Class II alpha and beta chain probes and several restriction enzymes did not correlate with either of the disease associated patterns. Several possibilities regarding the identity and mode of action of the two polypeptides are described.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cohen-Haguenauer O., Robbins E., Massart C., Busson M., Deschamps I., Hors J., Lalouel J. M., Dausset J., Cohen D. A systematic study of HLA class II-beta DNA restriction fragments in insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A. 1985 May;82(10):3335–3339. doi: 10.1073/pnas.82.10.3335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Festenstein H., Awad J., Hitman G. A., Cutbush S., Groves A. V., Cassell P., Ollier W., Sachs J. A. New HLA DNA polymorphisms associated with autoimmune diseases. Nature. 1986 Jul 3;322(6074):64–67. doi: 10.1038/322064a0. [DOI] [PubMed] [Google Scholar]
  3. Hitman G. A., Niven M. J., Festenstein H., Cassell P. G., Awad J., Walker-Smith J., Leonard J. N., Fry L., Ciclitira P., Kumar P. HLA class II alpha chain gene polymorphisms in patients with insulin-dependent diabetes mellitus, dermatitis herpetiformis, and celiac disease. J Clin Invest. 1987 Feb;79(2):609–615. doi: 10.1172/JCI112854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hitman G. A., Sachs J., Cassell P., Awad J., Bottazzo G. F., Tarn A. C., Schwartz G., Monson J. P., Festenstein H. A DR3-related DX alpha gene polymorphism strongly associates with insulin-dependent diabetes mellitus. Immunogenetics. 1986;23(1):47–51. doi: 10.1007/BF00376521. [DOI] [PubMed] [Google Scholar]
  5. Howell M. D., Austin R. K., Kelleher D., Nepom G. T., Kagnoff M. F. An HLA-D region restriction fragment length polymorphism associated with celiac disease. J Exp Med. 1986 Jul 1;164(1):333–338. doi: 10.1084/jem.164.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kunkel L. M., Smith K. D., Boyer S. H., Borgaonkar D. S., Wachtel S. S., Miller O. J., Breg W. R., Jones H. W., Jr, Rary J. M. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. doi: 10.1073/pnas.74.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Monaco J. J., McDevitt H. O. H-2-linked low-molecular weight polypeptide antigens assemble into an unusual macromolecular complex. 1984 Jun 28-Jul 4Nature. 309(5971):797–799. doi: 10.1038/309797a0. [DOI] [PubMed] [Google Scholar]
  8. Nepom B. S., Palmer J., Kim S. J., Hansen J. A., Holbeck S. L., Nepom G. T. Specific genomic markers for the HLA-DQ subregion discriminate between DR4+ insulin-dependent diabetes mellitus and DR4+ seropositive juvenile rheumatoid arthritis. J Exp Med. 1986 Jul 1;164(1):345–350. doi: 10.1084/jem.164.1.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Owerbach D., Lernmark A., Platz P., Ryder L. P., Rask L., Peterson P. A., Ludvigsson J. HLA-D region beta-chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulin-dependent diabetic individuals. Nature. 1983 Jun 30;303(5920):815–817. doi: 10.1038/303815a0. [DOI] [PubMed] [Google Scholar]
  10. Pujol-Borrell R., Todd I., Doshi M., Bottazzo G. F., Sutton R., Gray D., Adolf G. R., Feldmann M. HLA class II induction in human islet cells by interferon-gamma plus tumour necrosis factor or lymphotoxin. Nature. 1987 Mar 19;326(6110):304–306. doi: 10.1038/326304a0. [DOI] [PubMed] [Google Scholar]
  11. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  12. Spies T., Morton C. C., Nedospasov S. A., Fiers W., Pious D., Strominger J. L. Genes for the tumor necrosis factors alpha and beta are linked to the human major histocompatibility complex. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8699–8702. doi: 10.1073/pnas.83.22.8699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Stetler D., Grumet F. C., Erlich H. A. Polymorphic restriction endonuclease sites linked to the HLA-DR alpha gene: localization and use as genetic markers of insulin-dependent diabetes. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8100–8104. doi: 10.1073/pnas.82.23.8100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Zecher R., Ballhausen W., Reske K., Linder D., Schlüter M., Stirm S. The invariant chains of mouse class II antigens: biochemical properties and molecular relationship. Eur J Immunol. 1984 Jun;14(6):511–517. doi: 10.1002/eji.1830140606. [DOI] [PubMed] [Google Scholar]
  15. Zeliszewski D., Sterkers G., Choppin J., Freidel C., Gebuhrer L., Betuel H., Levy J. P. An antiviral T-cell clone defines a functional supertypic specificity shared by different HLA-DR molecules from DR2-short, DRw11, and DRw13 haplotypes. Immunogenetics. 1987;25(2):84–90. doi: 10.1007/BF00364272. [DOI] [PubMed] [Google Scholar]
  16. de Kretser T. A., Crumpton M. J., Bodmer J. G., Bodmer W. F. Demonstration of two distinct light chains in HLA-DR-associated antigens by two-dimensional gel electrophoresis. Eur J Immunol. 1982 Mar;12(3):214–221. doi: 10.1002/eji.1830120309. [DOI] [PubMed] [Google Scholar]

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