An Analysis of T cell receptor diversity in the NOD mouse: What can it tell us about the autoimmune process?

  • Adelaida Sarukhan
  • Henri-Jean Garchon
  • Claude Carnaud
Conference paper
Part of the NATO ASI Series book series (volume 80)

Abstract

Little is known concerning the features of the T cell receptor (TcR) repertoires which emerge in the course of cell-mediated autoimmune diseases. The finding of a highly restricted variable (V)α or Vβ usage by T cells from animals experimentally induced to respond to self antigens, such as myelin basic protein (MBP) (Acha-Orbea H., 1988) or type 2 collagen (David C.S., 1989, Chiocchia G., 1991), may not necessarily be true for spontaneously-triggered autoimmune reactions. In these reactions, the multiplicity of natural epitopes, the sequential release of sequestered antigens from damaged tissues and the aberrant expression of major histocompatibility complex (MHC) or costimulatory molecules on non-hematopietic cells may contribute to a rapid diversification of V gene usage. The question is important, not only from a theoretical, but also from a practical point of view since many strategies for the prevention of autoimmune diseases by modification of TcR expression are based on the assumption that, for a given individual and a given autoimmune disorder, the T cell repertoire is of sufficiently limited heterogeneity to warrant manipulation.

Keywords

Arthritis Electrophoresis Staphylococcus Transferase Mandel 

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References

  1. Acha-Orbea H, McDevitt HO (1987) The first external domain of the nonobese diabetic mouse class II I-A beta chain is unique. Proc. Natl. Acad. Sci. U. S. A. 84: 2435–2439PubMedCrossRefGoogle Scholar
  2. Acha-Orbea H, Mitchell DJ, Timmermann L, Wraith DC, Tausch GS, Waldor MK, Zamvil SS, McDevitt HO, Steinman L (1988) Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell 54: 263–273PubMedCrossRefGoogle Scholar
  3. Bacelj A, Charlton B, Koulmanda M, Mandel TE (1990) The role of V beta 8 cells in disease recurrence in isografts in diabetic NOD mice. Transplant. Proc. 22: 2167–2168PubMedGoogle Scholar
  4. Bacelj A, Charlton B, Mandel TE (1989) Prevention of cyclophosphamide-induced diabetes by anti-V beta 8 T-lymphocyte-receptor monoclonal antibody therapy in NOD/Wehi mice. Diabetes 38: 1492–1495PubMedCrossRefGoogle Scholar
  5. Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, Folli F, Richter-Olesen H, Camilli P (1990) Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 347: 151–156PubMedCrossRefGoogle Scholar
  6. Behlke M A, Chou HS, Huppi K, Loh DY (1986) Murine T-cell receptor mutants with deletions of beta-chain variable region genes. Proc. Natl. Acad. Sci. U. S. A. 83: 767–771PubMedCrossRefGoogle Scholar
  7. Bendelac A, Boitard C, Bach JF, Carnaud C (1989) Neonatal induction of allogeneic tolerance prevents T cell-mediated autoimmunity in NOD mice. Eur. J. Immunol. 19: 611–616PubMedCrossRefGoogle Scholar
  8. Bendelac A, Carnaud C, Boitard C, Bach JF (1987) Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt–2+ T cells. J. Exp. Med. 166: 823–832PubMedCrossRefGoogle Scholar
  9. Bohme J, Schuhbaur B, Kanagawa O, Benoist C, Mathis D (1990) MHC-linked protection from diabetes dissociated from clonal deletion of T cells. Science 249: 293–295PubMedCrossRefGoogle Scholar
  10. GF, Dean BM, McNally JM, Mackay EH, Swift PG, Gamble DR (1985) In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N. Engl. J. Med. 313: 353–360PubMedCrossRefGoogle Scholar
  11. Candeias S, Katz J, Benoist C, Mathis D, Haskins K (1991) Islet-specific T-cell clones from nonobese diabetic mice express heterogeneous T-cell receptors. Proc. Natl. Acad. Sci. U. S. A. 88: 6167–6170PubMedCrossRefGoogle Scholar
  12. Candeias S, Waltzinger C, Benoist C, Mathis D (1991) The Vbeta 17+ T cell repertoire: skewed J beta usage after thymic selection: dissimilar CDR3s in CD4+ versus CD8+ cells J. Exp. Med. 174: 989–1000PubMedCrossRefGoogle Scholar
  13. Casanova JL, Cerottini JC, Matthes M, Necker A, Gournier H, Barra C, Widmann C, Macdonald R, Lemonnier F, Malissen B, Maryanski JL (1992) H-2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors of limited diversity. J. Exp. Med. 176: 439–447PubMedCrossRefGoogle Scholar
  14. Chiocchia G, Boissier MC, Fournier C (1991) Therapy against murine collagen-induced arthritis with T cell receptor V beta-specific antibodies. Eur. J. Immunol. 12: 2899–2905CrossRefGoogle Scholar
  15. Choi Y, Kappler JW, Marrack P (1991) A superantigen encoded in the open reading frame of the 3’ long terminal repeat of mouse mammary tumour virus. Nature 350: 203–207PubMedCrossRefGoogle Scholar
  16. David CS, Banerjee S (1989) T cell receptor genes and disease susceptibility. Arthritis. Rheum. 32: 105–107PubMedCrossRefGoogle Scholar
  17. Davis MM, Bjorkman PJ (1988) T-cell antigen receptor genes and T-cell recognition. Nature 334: 395–402PubMedCrossRefGoogle Scholar
  18. Dellabona P, Peccoud J, Kappler J, Marrack P, Benoist C, Mathis D (1990) Superantigens interact with MHC class II molecules outside of the antigen groove. Cell 62: 1115–1121PubMedCrossRefGoogle Scholar
  19. Edouard P, Thivolet C, Bedossa P, Olivi M, Legrand B, Bendelac A, Bach JF, Carnaud C (1993) Evidence for a preferential V beta usage by the T cells which adoptively transfer diabetes in NOD mice. Eur. J. Immunol. 23: 727–733PubMedCrossRefGoogle Scholar
  20. Elias D, Markovits D, Reshel T, Van der Zee R, Cohen IR (1990) Induction and therapy of autoimmune diabetes in the non-obese diabetic (NOD/Lt) mouse by a 65kDa heat shock protein. Proc. Natl. Acad. Sci. U.S.A. 4: 1576–1580CrossRefGoogle Scholar
  21. Feeney AJ (1991) Junctional sequences of fetal T cell receptor b chains have few N regions. J. Exp. Med. 174: 115–124.PubMedCrossRefGoogle Scholar
  22. Fairchild S, Knight AM, Dyson PJ, Tomonari K (1991) Co-segregation of a gene encoding a deletion ligand for Tcrb-V3+ T cells with Mtv-3. Immunogenetics 34: 227–230PubMedCrossRefGoogle Scholar
  23. Fukuda M, Horio F, Kubo R, Hattori M (1989) Monoclonal antibody F23.1 against T cell bearing VJS8 TCR elements can prevent the development of insulitis in NOD mice. Diabetes 38 (suppl):12 AGoogle Scholar
  24. Hayward AR, Shreiber M (1989) Neonatal injection of CD3 antibody into nonobese diabetic mice reduces the incidence of insulitis and diabetes. J. Immunol. 143: 1555–1559PubMedGoogle Scholar
  25. Howe ML, Goldstein AL, Battisto JR (1970) Isogeneic lymphocyteinteractions: recognition of self antigens by cells of the neonqtal thymus. Proc. Natl. Acad. Sci. USA 67: 613–619.PubMedCrossRefGoogle Scholar
  26. Janeway CA JR, Yagi J, Contrad PJ, Katz ME, Jones B, Uroegop S, Buxser S (1989) T-cell responses to Mis and to bacterial proteins that mimic its behavior. Immunol. Rev. 6: 61–88CrossRefGoogle Scholar
  27. Jorgensen JL, Esser U, Fazekas de St. Groth B, Reay PA, Davis MM (1992) Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics. Nature 355: 224–230.Google Scholar
  28. Kabat EA, Wu TT, Reid Miller M, Perry HM, Gottesman KS (1987) Sequences of proteins of immunological interest. Department of Health and Human Services, Bethesda, MD, USA, 4th edition.Google Scholar
  29. Kappler JW, Roehm N, Marrack P (1987) T cell tolerance by clonal elimination in the thymus. Cell 49: 273–280PubMedCrossRefGoogle Scholar
  30. Kawabe Y, Ochi A (1991) Programmed cell death and extra thymic reduction of Vbeta8+ CD4+ T cells in mice tolerant to Staphylococcus aureus enterotoxin B. Nature 349: 245–248PubMedCrossRefGoogle Scholar
  31. Leiter E H (1989) The genetics of diabetes susceptibility in mice. FASEB. J. 3: 2231–2241Google Scholar
  32. Loh E Y, Elliott J F, Cwirla S, Lanier L L, Davis M M (1989) Polymerase chain reaction with single-sided specificity: analysis of T cell receptor delta chain. Science 243: 217–220PubMedCrossRefGoogle Scholar
  33. Louie M C, Nelson C A, Loh D Y (1989) Identification and characterization of new murine T cell receptor beta chain variable region (V beta) genes. J. Exp. Med. 170: 1987–1998PubMedCrossRefGoogle Scholar
  34. Lund T, O’Reilly L, Hutchings P, Kanagawa O, Simpson E, Gravely R, Chandler P, Dyson J, Picard JK, Edwards A, Kioussis D, Cooke A (1990) Prevention of insulin-dependent diabetes mellitus in non-obese diabetic mice by transgenes encoding modified I–A beta–chain or normal I-E alpha-chain. Nature 345: 727–729PubMedCrossRefGoogle Scholar
  35. Maeda T, Sumida T, Kurasawa K, Tomioka H, Itoh I, Yoshida S, Koike T (1991) T-lymphocyte-receptor repertoire of infiltrating T lymphocytes into NOD mouse pancreas. Diabetes 40: 1580–1585PubMedCrossRefGoogle Scholar
  36. Makino S, Kimimoto K, Muraoka Y, Mizushima Y, Kahagiri K, Tochino Y (1980) Breeding of a non-obese, diabetic strain of mice. Exp. Anim. 1: 1–13Google Scholar
  37. McDuffie M, Schweiger D, Reitz B, Ostrowska A, Knight AM, Dyson PJ (1992) I-E-independent deletion of V beta 17a+ T cells by Mtv-3 from the nonobese diabetic mouse. J. Immunol. 148: 2097–2102PubMedGoogle Scholar
  38. Miyazaki A, Hanafusa T, Yamada K, Miyagawa J, Fujino-Kurihara H, Nakajima H, Nonaka K, Tarui S (1985) Predominance of T lymphocytes in pancreatic islets and spleen of pre-diabetic non-obese diabetic (NOD) mice: a longitudinal study. Clin. Exp. Immunol. 60: 622–630PubMedGoogle Scholar
  39. Nakano N, Kikutani H, Nishimoto H, Kishimoto T (1991) T cell receptor V gene usage of islet beta cell–reactive T cells is not restricted in non-obese diabetic mice. J. Exp. Med. 173: 1091–1097PubMedCrossRefGoogle Scholar
  40. Nepom GT (1990) HLA and type I diabetes. Immunol. Today 9: 314–315CrossRefGoogle Scholar
  41. Nishimoto H, Kikutani H, Yamamura K, Kishimoto T (1987) Prevention of autoimmune insulitis by expression of I-E molecules in NOD mice. Nature 328: 432–434PubMedCrossRefGoogle Scholar
  42. O’Reilly L A, Hutchings P R, Crocker P R, Simpson E, Lund T, Kioussis D, Takei F, Baird J, Cooke A (1991) Characterization of pancreatic islet cell infiltrates in NOD mice: effect of cell transfer and transgene expression. Eur. J. Immunol. 21: 1171–1180PubMedCrossRefGoogle Scholar
  43. Oshi A, Migita K, Yuh K (1992) Do anergic T cells live or die? Res. Immunol. 143: 304–306CrossRefGoogle Scholar
  44. Prud’homme GJ, Long TY, Bocarro DC, Balderas RS, Theofilopoulos AN (1991) Analysis of pancreas-infiltrating T cells in diabetic NOD mice: fusion with BW5147 yields a high frequency of islet-reactive hybridomas. Autoimmunity 10: 285–289PubMedCrossRefGoogle Scholar
  45. Rammensee HG, Kroschewski R, Frangoulis B (1989) Clonal anergy induced in mature V beta 6+ T lymphocytes on immunizing Mls-lb mice with Mls-1a expressing cells. Nature 339: 541–544PubMedCrossRefGoogle Scholar
  46. Riggs JE; Stowers RS Mosier DE (1991) Adoptive transfer of neonatal T lymphocytes rescues immunoglobulin production in mice with severe combined immune deficiency. J. Exp. Med. 173: 265–268PubMedCrossRefGoogle Scholar
  47. Schneider R, Lees RK, Pedrazzini T, Zinkernagel RM, Hengartner H, MacDonald HR (1989) Postnatal disappearance of self-reactive (V beta 6+) cells from the thymus of Mlsa mice. Implications for T cell development and autoimmunity. J. Exp. Med. l69: 2149–2158CrossRefGoogle Scholar
  48. Singer PA, Theofilopoulos AN (1990) T-cell receptor V beta repertoire expression in murine models of SLE. Immunol. Rev. 144: 103–127CrossRefGoogle Scholar
  49. Six A, Jouvin-Marche E, Loh DY, Cazenave PA, Marche PN (1991) Identification of a T cell receptor beta chain variable region, V beta 20, that is differentially expressed in various strains of mice. J. Exp. Med. 174: 1263–12PubMedCrossRefGoogle Scholar
  50. Tomonari K, Fairchild S, Rosenwasser OA (1993) Influence of viral superantigens on VP-and Va-specific positive and negative selection. Immunol Rev 131: 131–168PubMedCrossRefGoogle Scholar
  51. Wade T, Bill J, Marrack PC, Palmer E, Kappler JW (1988) Molecular basis for the nonexpression of V beta 17 in some strains of mice. J. Immunol. 141: 2165–2167PubMedGoogle Scholar
  52. Waters S H, O’Neil JJ, Melican DT, Appel MC (1992) Multiple TCR V beta usage by infiltrates of young NOD mouse islets of Langerhans. A polymerase chain reaction analysis. Diabetes 41:308–312Webb SR, Sprent J (1990) Response of mature unprimed CD8+ T cells to Mlsa determinants. J. Exp. Med. 171: 953–958Google Scholar
  53. Zhang XM, Heber-Katz E (1992) T cell receptor sequences from encephalitogenic T cells in adult Lewis rats suggest an early ontogenic origin. J. Immunol. 148: 746–752PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • Adelaida Sarukhan
    • 1
  • Henri-Jean Garchon
    • 1
  • Claude Carnaud
    • 1
  1. 1.INSERM U 25Hôpital NeckerParis Cedex 15France

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