Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Feb;91(2):226–231. doi: 10.1111/j.1365-2249.1993.tb05887.x

T cell receptor haplotypes in families of patients with insulin-dependent diabetes mellitus.

H Kelly 1, M J Garlepp 1
PMCID: PMC1554681  PMID: 8094039

Abstract

The frequencies of Bgl 11 and BamH1 restriction fragment length polymorphisms (RFLP) of C beta, V beta 8, V beta 11 and V beta 7.2 have been defined in a healthy Australian population. Linkage disequilibrium between alleles of the T cell receptor (TCR) V beta 8 and V beta 11 gene segments has been confirmed. We have also confirmed the lack of linkage disequilibrium between either of these loci and alleles at C beta or V beta 7.2. Using RFLPs at V beta 11 and V beta 8 loci TCR beta haplotypes have been identified in five families in which the probands have insulin-dependent diabetes mellitus (IDDM). An extremely rare haplotype, marked by the higher molecular weight BamH1 allele (H, H) at each of V beta 11 and V beta 8, was found in the DR4+ DR3- probands of two families (P = 0.004). In three families in which the probands had DR3, the more common TCR haplotype LH (V beta 11, V beta 8) was found. Taken together, these data confirm that linkage disequilibrium does exist in the TCR beta locus, at least in some regions, and suggest that detailed analysis of the relationship between TCR V beta haplotypes and HLA is warranted since these RFLPs may be markers for important allelic V gene sequence variations.

Full text

PDF
226

Selected References

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

  1. Awdeh Z. L., Alper C. A. Inherited structural polymorphism of the fourth component of human complement. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3576–3580. doi: 10.1073/pnas.77.6.3576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beall S. S., Concannon P., Charmley P., McFarland H. F., Gatti R. A., Hood L. E., McFarlin D. E., Biddison W. E. The germline repertoire of T cell receptor beta-chain genes in patients with chronic progressive multiple sclerosis. J Neuroimmunol. 1989 Jan;21(1):59–66. doi: 10.1016/0165-5728(89)90159-8. [DOI] [PubMed] [Google Scholar]
  3. Castaño L., Eisenbarth G. S. Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol. 1990;8:647–679. doi: 10.1146/annurev.iy.08.040190.003243. [DOI] [PubMed] [Google Scholar]
  4. Charmley P., Chao A., Concannon P., Hood L., Gatti R. A. Haplotyping the human T-cell receptor beta-chain gene complex by use of restriction fragment length polymorphisms. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4823–4827. doi: 10.1073/pnas.87.12.4823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Charmley P., Concannon P., Gatti R. A. T-cell receptor beta-chain DNA polymorphism frequencies in healthy HLA-DR homozygotes. Tissue Antigens. 1990 Apr;35(4):157–164. doi: 10.1111/j.1399-0039.1990.tb01773.x. [DOI] [PubMed] [Google Scholar]
  6. Christmas T. I., Manning L. S., Davis M. R., Robinson B. W., Garlepp M. J. HLA antigen expression and malignant mesothelioma. Am J Respir Cell Mol Biol. 1991 Sep;5(3):213–220. doi: 10.1165/ajrcmb/5.3.213. [DOI] [PubMed] [Google Scholar]
  7. Concannon P., Gatti R. A., Hood L. E. Human T cell receptor V beta gene polymorphism. J Exp Med. 1987 Apr 1;165(4):1130–1140. doi: 10.1084/jem.165.4.1130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Concannon P., Wright J. A., Wright L. G., Sylvester D. R., Spielman R. S. T-cell receptor genes and insulin-dependent diabetes mellitus (IDDM): no evidence for linkage from affected sib pairs. Am J Hum Genet. 1990 Jul;47(1):45–52. [PMC free article] [PubMed] [Google Scholar]
  9. Cox N. J., Spielman R. S. The insulin gene and susceptibility to IDDM. Genet Epidemiol. 1989;6(1):65–69. doi: 10.1002/gepi.1370060113. [DOI] [PubMed] [Google Scholar]
  10. Fugger L., Sandberg-Wollheim M., Morling N., Ryder L. P., Svejgaard A. The germline repertoire of T-cell receptor beta chain genes in patients with relapsing/remitting multiple sclerosis or optic neuritis. Immunogenetics. 1990;31(4):278–280. doi: 10.1007/BF00204901. [DOI] [PubMed] [Google Scholar]
  11. Hoover M. L., Angelini G., Ball E., Stastny P., Marks J., Rosenstock J., Raskin P., Ferrara G. B., Tosi R., Capra J. D. HLA-DQ and T-cell receptor genes in insulin-dependent diabetes mellitus. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 2):803–809. doi: 10.1101/sqb.1986.051.01.093. [DOI] [PubMed] [Google Scholar]
  12. Ito M., Tanimoto M., Kamura H., Yoneda M., Morishima Y., Takatsuki K., Itatsu T., Saito H. Association of HLA-DR phenotypes and T-lymphocyte-receptor beta-chain-region RFLP with IDDM in Japanese. Diabetes. 1988 Dec;37(12):1633–1636. doi: 10.2337/diab.37.12.1633. [DOI] [PubMed] [Google Scholar]
  13. Jorgensen J. L., Esser U., Fazekas de St Groth B., Reay P. A., Davis M. M. Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics. Nature. 1992 Jan 16;355(6357):224–230. doi: 10.1038/355224a0. [DOI] [PubMed] [Google Scholar]
  14. Julier C., Hyer R. N., Davies J., Merlin F., Soularue P., Briant L., Cathelineau G., Deschamps I., Rotter J. I., Froguel P. Insulin-IGF2 region on chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. Nature. 1991 Nov 14;354(6349):155–159. doi: 10.1038/354155a0. [DOI] [PubMed] [Google Scholar]
  15. Kelly H., McCann V. J., Kay P. H., Dawkins R. L. Susceptibility to IDDM is marked by MHC supratypes rather than individual alleles. Immunogenetics. 1985;22(6):643–651. doi: 10.1007/BF00430313. [DOI] [PubMed] [Google Scholar]
  16. McMillan S. A., Graham C. A., Hart P. J., Hadden D. R., McNeill T. A. A T cell receptor beta chain polymorphism is associated with patients developing insulin-dependent diabetes after the age of 20 years. Clin Exp Immunol. 1990 Dec;82(3):538–541. doi: 10.1111/j.1365-2249.1990.tb05486.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Millward B. A., Welsh K. I., Leslie R. D., Pyke D. A., Demaine A. G. T cell receptor beta chain polymorphisms are associated with insulin-dependent diabetes. Clin Exp Immunol. 1987 Oct;70(1):152–157. [PMC free article] [PubMed] [Google Scholar]
  18. Nepom G. T., Erlich H. MHC class-II molecules and autoimmunity. Annu Rev Immunol. 1991;9:493–525. doi: 10.1146/annurev.iy.09.040191.002425. [DOI] [PubMed] [Google Scholar]
  19. Nerup J., Platz P., Andersen O. O., Christy M., Lyngsoe J., Poulsen J. E., Ryder L. P., Nielsen L. S., Thomsen M., Svejgaard A. HL-A antigens and diabetes mellitus. Lancet. 1974 Oct 12;2(7885):864–866. doi: 10.1016/s0140-6736(74)91201-x. [DOI] [PubMed] [Google Scholar]
  20. Posnett D. N. Allelic variations of human TCR V gene products. Immunol Today. 1990 Oct;11(10):368–373. doi: 10.1016/0167-5699(90)90143-w. [DOI] [PubMed] [Google Scholar]
  21. Robinson M. A. Allelic sequence variations in the hypervariable region of a T-cell receptor beta chain: correlation with restriction fragment length polymorphism in human families and populations. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9422–9426. doi: 10.1073/pnas.86.23.9422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Singal D. P., Blajchman M. A. Histocompatibility (HL-A) antigens, lymphocytotoxic antibodies and tissue antibodies in patients with diabetes mellitus. Diabetes. 1973 Jun;22(6):429–432. doi: 10.2337/diab.22.6.429. [DOI] [PubMed] [Google Scholar]
  23. Spielman R. S., Baur M. P., Clerget-Darpoux F. Genetic analysis of IDDM: summary of GAW5 IDDM results. Genet Epidemiol. 1989;6(1):43–58. doi: 10.1002/gepi.1370060111. [DOI] [PubMed] [Google Scholar]
  24. Thomson G., Robinson W. P., Kuhner M. K., Joe S., Klitz W. HLA and insulin gene associations with IDDM. Genet Epidemiol. 1989;6(1):155–160. doi: 10.1002/gepi.1370060129. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES