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J Exp Med. 1991 September 1; 174(3): 633–638.
PMCID: PMC2118938

Genetic dissection of T cell receptor V beta gene requirements for spontaneous murine diabetes

Abstract

It has been demonstrated, in certain autoimmune disease models, that pathogenic T cells express antigen receptors of limited diversity. It has been suggested that the T cells responsible for the pathogenesis of type I diabetes mellitus might similarly demonstrate restricted T cell receptor (TCR) usage. Recently, attempts have been made to identify the V beta subset(s) that initiates and/or perpetuates the antiislet response in a mouse model of spontaneous autoimmune diabetes (non-obese diabetic [NOD] mice). In studies reported here, we have bred NOD mice to a mouse strain that congenitally lacks approximately one-half of the conventional TCR V beta alleles. Included in this deletion are TCR V beta gene products previously implicated as being involved in the pathogenesis of NOD disease. By studying second backcross-intercross animals, we were able to demonstrate that this deletion of TCR V beta gene segments did not prevent the development of insulitis or diabetes.

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Selected References

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  • Shizuru JA, Taylor-Edwards C, Banks BA, Gregory AK, Fathman CG. Immunotherapy of the nonobese diabetic mouse: treatment with an antibody to T-helper lymphocytes. Science. 1988 Apr 29;240(4852):659–662. [PubMed]
  • Wang Y, Hao L, Gill RG, Lafferty KJ. Autoimmune diabetes in NOD mouse is L3T4 T-lymphocyte dependent. Diabetes. 1987 Apr;36(4):535–538. [PubMed]
  • Zamvil SS, Mitchell DJ, Lee NE, Moore AC, Waldor MK, Sakai K, Rothbard JB, McDevitt HO, Steinman L, Acha-Orbea H. Predominant expression of a T cell receptor V beta gene subfamily in autoimmune encephalomyelitis. J Exp Med. 1988 May 1;167(5):1586–1596. [PMC free article] [PubMed]
  • Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med. 1986 May 22;314(21):1360–1368. [PubMed]
  • Rossini AA, Mordes JP, Like AA. Immunology of insulin-dependent diabetes mellitus. Annu Rev Immunol. 1985;3:289–320. [PubMed]
  • Krolewski AS, Warram JH, Rand LI, Kahn CR. Epidemiologic approach to the etiology of type I diabetes mellitus and its complications. N Engl J Med. 1987 Nov 26;317(22):1390–1398. [PubMed]
  • Prochazka M, Leiter EH, Serreze DV, Coleman DL. Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice. Science. 1987 Jul 17;237(4812):286–289. [PubMed]
  • Wicker LS, Miller BJ, Coker LZ, McNally SE, Scott S, Mullen Y, Appel MC. Genetic control of diabetes and insulitis in the nonobese diabetic (NOD) mouse. J Exp Med. 1987 Jun 1;165(6):1639–1654. [PMC free article] [PubMed]
  • Bacelj A, Charlton B, Mandel TE. Prevention of cyclophosphamide-induced diabetes by anti-V beta 8 T-lymphocyte-receptor monoclonal antibody therapy in NOD/Wehi mice. Diabetes. 1989 Nov;38(11):1492–1495. [PubMed]
  • Behlke MA, Chou HS, Huppi K, Loh DY. Murine T-cell receptor mutants with deletions of beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986 Feb;83(3):767–771. [PubMed]
  • Staerz UD, Rammensee HG, Benedetto JD, Bevan MJ. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. J Immunol. 1985 Jun;134(6):3994–4000. [PubMed]
  • Behlke MA, Henkel TJ, Anderson SJ, Lan NC, Hood L, Braciale VL, Braciale TJ, Loh DY. Expression of a murine polyclonal T cell receptor marker correlates with the use of specific members of the V beta 8 gene segment subfamily. J Exp Med. 1987 Jan 1;165(1):257–262. [PMC free article] [PubMed]
  • Kappler JW, Wade T, White J, Kushnir E, Blackman M, Bill J, Roehm N, Marrack P. A T cell receptor V beta segment that imparts reactivity to a class II major histocompatibility complex product. Cell. 1987 Apr 24;49(2):263–271. [PubMed]
  • Wade T, Bill J, Marrack PC, Palmer E, Kappler JW. Molecular basis for the nonexpression of V beta 17 in some strains of mice. J Immunol. 1988 Sep 15;141(6):2165–2167. [PubMed]
  • Symington FW, Sprent J. A monoclonal antibody detecting an Ia specificity mapping in the I-A or I-E subregion. Immunogenetics. 1981;14(1-2):53–61. [PubMed]
  • Bayer EA, Wilchek M. The use of the avidin-biotin complex as a tool in molecular biology. Methods Biochem Anal. 1980;26:1–45. [PubMed]
  • Ledbetter JA, Herzenberg LA. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. [PubMed]
  • Livingstone A, Edwards CT, Shizuru JA, Fathman CG. Genetic analysis of diabetes in the nonobese diabetic mouse. I. MHC and T cell receptor beta gene expression. J Immunol. 1991 Jan 15;146(2):529–534. [PubMed]
  • Wicker LS, Miller BJ, Mullen Y. Transfer of autoimmune diabetes mellitus with splenocytes from nonobese diabetic (NOD) mice. Diabetes. 1986 Aug;35(8):855–860. [PubMed]
  • Wicker LS, Miller BJ, Fischer PA, Pressey A, Peterson LB. Genetic control of diabetes and insulitis in the nonobese diabetic mouse. Pedigree analysis of a diabetic H-2nod/b heterozygote. J Immunol. 1989 Feb 1;142(3):781–784. [PubMed]
  • Acha-Orbea H, Steinman L, McDevitt HO. T cell receptors in murine autoimmune diseases. Annu Rev Immunol. 1989;7:371–405. [PubMed]
  • Kumar V, Kono DH, Urban JL, Hood L. The T-cell receptor repertoire and autoimmune diseases. Annu Rev Immunol. 1989;7:657–682. [PubMed]
  • Fry AM, Matis LA. Self-tolerance alters T-cell receptor expression in an antigen-specific MHC restricted immune response. Nature. 1988 Oct 27;335(6193):830–832. [PubMed]
  • Fry AM, Cotterman MM, Matis LA. The influence of self-MHC and non-MHC antigens on the selection of an antigen-specific T cell receptor repertoire. J Immunol. 1989 Oct 15;143(8):2723–2729. [PubMed]
  • Frangoulis B, Pla M, Rammensee HG. Alternative T cell receptor gene usage induced by self tolerance. Eur J Immunol. 1989 Mar;19(3):553–555. [PubMed]
  • Falcioni F, Dembic Z, Muller S, Lehmann PV, Nagy ZA. Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin. J Exp Med. 1990 May 1;171(5):1665–1681. [PMC free article] [PubMed]
  • Ruberti G, Gaur A, Fathman CG, Livingstone AM. The T cell receptor repertoire influences V beta element usage in response to myoglobin. J Exp Med. 1991 Jul 1;174(1):83–92. [PMC free article] [PubMed]

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