• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jul 15, 1991; 88(14): 6167–6170.

Islet-specific T-cell clones from nonobese diabetic mice express heterogeneous T-cell receptors.


Nonobese diabetic (NOD) mice spontaneously develop a T-cell-mediated autoimmune disease that is similar in many respects to insulin-dependent diabetes mellitus in humans. T-cell clones that specifically recognize pancreatic islet cell antigens can be derived from NOD mice, and most of these have been diabetogenic upon transfer to healthy recipients. We report herein the sequences of the T-cell receptor alpha and beta chains from four NOD-derived, islet-specific clones. The sequences are quite heterogeneous--in the junctional regions, specifically--so there seems to be little hope for treating this disease with specific anti-T-cell receptor reagents. This result contrasts with the strikingly restricted junctional region sequences reported for the receptors on clones derived from mice with experimental allergic encephalomyelitis, another T-cell-mediated autoimmune disease. We discuss possible explanations for this difference.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (724K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol. 1990;8:579–621. [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]
  • Acha-Orbea H, Mitchell DJ, Timmermann L, Wraith DC, Tausch GS, Waldor MK, Zamvil SS, McDevitt HO, Steinman L. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell. 1988 Jul 15;54(2):263–273. [PubMed]
  • Urban JL, Kumar V, Kono DH, Gomez C, Horvath SJ, Clayton J, Ando DG, Sercarz EE, Hood L. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell. 1988 Aug 12;54(4):577–592. [PubMed]
  • Howell MD, Winters ST, Olee T, Powell HC, Carlo DJ, Brostoff SW. Vaccination against experimental allergic encephalomyelitis with T cell receptor peptides. Science. 1989 Nov 3;246(4930):668–670. [PubMed]
  • Vandenbark AA, Hashim G, Offner H. Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature. 1989 Oct 12;341(6242):541–544. [PubMed]
  • Castaño L, Eisenbarth GS. Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol. 1990;8:647–679. [PubMed]
  • Haskins K, Portas M, Bradley B, Wegmann D, Lafferty K. T-lymphocyte clone specific for pancreatic islet antigen. Diabetes. 1988 Oct;37(10):1444–1448. [PubMed]
  • Haskins K, Portas M, Bergman B, Lafferty K, Bradley B. Pancreatic islet-specific T-cell clones from nonobese diabetic mice. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8000–8004. [PMC free article] [PubMed]
  • Haskins K, McDuffie M. Acceleration of diabetes in young NOD mice with a CD4+ islet-specific T cell clone. Science. 1990 Sep 21;249(4975):1433–1436. [PubMed]
  • Louie MC, Nelson CA, Loh DY. Identification and characterization of new murine T cell receptor beta chain variable region (V beta) genes. J Exp Med. 1989 Dec 1;170(6):1987–1998. [PMC free article] [PubMed]
  • Yague J, Blackman M, Born W, Marrack P, Kappler J, Palmer E. The structure of V alpha and J alpha segments in the mouse. Nucleic Acids Res. 1988 Dec 9;16(23):11355–11364. [PMC free article] [PubMed]
  • Wilson RK, Lai E, Concannon P, Barth RK, Hood LE. Structure, organization and polymorphism of murine and human T-cell receptor alpha and beta chain gene families. Immunol Rev. 1988 Jan;101:149–172. [PubMed]
  • Reich EP, Sherwin RS, Kanagawa O, Janeway CA., Jr An explanation for the protective effect of the MHC class II I-E molecule in murine diabetes. Nature. 1989 Sep 28;341(6240):326–328. [PubMed]
  • Böhme J, Schuhbaur B, Kanagawa O, Benoist C, Mathis D. MHC-linked protection from diabetes dissociated from clonal deletion of T cells. Science. 1990 Jul 20;249(4966):293–295. [PubMed]
  • Oksenberg JR, Stuart S, Begovich AB, Bell RB, Erlich HA, Steinman L, Bernard CC. Limited heterogeneity of rearranged T-cell receptor V alpha transcripts in brains of multiple sclerosis patients. Nature. 1990 May 24;345(6273):344–346. [PubMed]
  • Tan KN, Datlof BM, Gilmore JA, Kronman AC, Lee JH, Maxam AM, Rao A. The T cell receptor V alpha 3 gene segment is associated with reactivity to p-azobenzenearsonate. Cell. 1988 Jul 15;54(2):247–261. [PubMed]
  • Yanagi Y, Maekawa R, Cook T, Kanagawa O, Oldstone MB. Restricted V-segment usage in T-cell receptors from cytotoxic T lymphocytes specific for a major epitope of lymphocytic choriomeningitis virus. J Virol. 1990 Dec;64(12):5919–5926. [PMC free article] [PubMed]
  • Fink PJ, Matis LA, McElligott DL, Bookman M, Hedrick SM. Correlations between T-cell specificity and the structure of the antigen receptor. Nature. 1986 May 15;321(6067):219–226. [PubMed]
  • Hochgeschwender U, Simon HG, Weltzien HU, Bartels F, Becker A, Epplen JT. Dominance of one T-cell receptor in the H-2Kb/TNP response. Nature. 1987 Mar 19;326(6110):307–309. [PubMed]
  • Aebischer T, Oehen S, Hengartner H. Preferential usage of V alpha 4 and V beta 10 T cell receptor genes by lymphocytic choriomeningitis virus glycoprotein-specific H-2Db-restricted cytotoxic T cells. Eur J Immunol. 1990 Mar;20(3):523–531. [PubMed]
  • Danska JS, Livingstone AM, Paragas V, Ishihara T, Fathman CG. The presumptive CDR3 regions of both T cell receptor alpha and beta chains determine T cell specificity for myoglobin peptides. J Exp Med. 1990 Jul 1;172(1):27–33. [PMC free article] [PubMed]
  • Sherman DH, Hochman PS, Dick R, Tizard R, Ramachandran KL, Flavell RA, Huber BT. Molecular analysis of antigen recognition by insulin-specific T-cell hybridomas from B6 wild-type and bm12 mutant mice. Mol Cell Biol. 1987 May;7(5):1865–1872. [PMC free article] [PubMed]
  • Spinella DG, Hansen TH, Walsh WD, Behlke MA, Tillinghast JP, Chou HS, Whiteley PJ, Kapp JA, Pierce CW, Shevach EM, et al. Receptor diversity of insulin-specific T cell lines from C57BL (H-2b) mice. J Immunol. 1987 Jun 1;138(11):3991–3995. [PubMed]
  • Iwamoto A, Ohashi PS, Pircher H, Walker CL, Michalopoulos EE, Rupp F, Hengartner H, Mak TW. T cell receptor variable gene usage in a specific cytotoxic T cell response. Primary structure of the antigen-MHC receptor of four hapten-specific cytotoxic T cell clones. J Exp Med. 1987 Mar 1;165(3):591–600. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences