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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Aug 1;176(2):381–388. doi: 10.1084/jem.176.2.381

Expression of a transgenic T cell receptor beta chain enhances collagen- induced arthritis

PMCID: PMC2119315  PMID: 1386871

Abstract

SWR/J transgenic (tg) mice were generated expressing the TCR beta chain derived from an anticollagen type II (CII) arthritogenic T cell clone. The SWR/J strain was selected because it is resistant to collagen- induced arthritis (CIA) and lacks the V beta gene segment used by the T cell clone. Expression of the tg beta chain on all thymocytes and peripheral lymph node T cells led to a more efficient anti-CII immune response, but did not confer CIA susceptibility to SWR/J mice. Nevertheless, this tg beta chain enhanced predisposition to CIA as (DBA/1 x SWR) F1 beta tg mice were more susceptible than normal F1 littermates. Our results demonstrate that the expression of the tg beta chain contributes to CIA susceptibility, but by itself it is not sufficient to overcome CIA resistance in the SWR/J strain.

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Selected References

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  1. Anderson G. D., Banerjee S., Luthra H. S., David C. S. Role of Mls-1 locus and clonal deletion of T cells in susceptibility to collagen-induced arthritis in mice. J Immunol. 1991 Aug 15;147(4):1189–1193. [PubMed] [Google Scholar]
  2. Andersson M., Cremer M. A., Terato K., Burkhardt H., Holmdahl R. Analysis of type II collagen reactive T cells in the mouse. II. Different localization of immunodominant T cell epitopes on heterologous and autologous type II collagen. Scand J Immunol. 1991 May;33(5):505–510. doi: 10.1111/j.1365-3083.1991.tb02520.x. [DOI] [PubMed] [Google Scholar]
  3. Andersson M., Goldschmidt T. J., Michaelsson E., Larsson A., Holmdahl R. T-cell receptor V beta haplotype and complement component C5 play no significant role for the resistance to collagen-induced arthritis in the SWR mouse. Immunology. 1991 Jun;73(2):191–196. [PMC free article] [PubMed] [Google Scholar]
  4. Banerjee S., Anderson G. D., Luthra H. S., David C. S. Influence of complement C5 and V beta T cell receptor mutations on susceptibility to collagen-induced arthritis in mice. J Immunol. 1989 Apr 1;142(7):2237–2243. [PubMed] [Google Scholar]
  5. Banerjee S., Haqqi T. M., Luthra H. S., Stuart J. M., David C. S. Possible role of V beta T cell receptor genes in susceptibility to collagen-induced arthritis in mice. J Exp Med. 1988 Mar 1;167(3):832–839. doi: 10.1084/jem.167.3.832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Behlke M. A., Chou H. S., Huppi K., Loh D. Y. 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. doi: 10.1073/pnas.83.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cathcart E. S., Hayes K. C., Gonnerman W. A., Lazzari A. A., Franzblau C. Experimental arthritis in a nonhuman primate. I. Induction by bovine type II collagen. Lab Invest. 1986 Jan;54(1):26–31. [PubMed] [Google Scholar]
  8. Chiocchia G., Boissier M. C., Fournier C. Therapy against murine collagen-induced arthritis with T cell receptor V beta-specific antibodies. Eur J Immunol. 1991 Dec;21(12):2899–2905. doi: 10.1002/eji.1830211202. [DOI] [PubMed] [Google Scholar]
  9. Courtenay J. S., Dallman M. J., Dayan A. D., Martin A., Mosedale B. Immunisation against heterologous type II collagen induces arthritis in mice. Nature. 1980 Feb 14;283(5748):666–668. doi: 10.1038/283666a0. [DOI] [PubMed] [Google Scholar]
  10. Duby A. D., Sinclair A. K., Osborne-Lawrence S. L., Zeldes W., Kan L., Fox D. A. Clonal heterogeneity of synovial fluid T lymphocytes from patients with rheumatoid arthritis. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6206–6210. doi: 10.1073/pnas.86.16.6206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eichmann K., Falk I., Melchers I., Simon M. M. Quantitative studies on T cell diversity. I. Determination of the precursor frequencies for two types of streptococcus A-specific helper cells in nonimmune, polyclonally activated splenic T cells. J Exp Med. 1980 Sep 1;152(3):477–492. doi: 10.1084/jem.152.3.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goldschmidt T. J., Jansson L., Holmdahl R. In vivo elimination of T cells expressing specific T-cell receptor V beta chains in mice susceptible to collagen-induced arthritis. Immunology. 1990 Apr;69(4):508–514. [PMC free article] [PubMed] [Google Scholar]
  13. Haqqi T. M., Banerjee S., Anderson G. D., David C. S. RIII S/J (H-2r). An inbred mouse strain with a massive deletion of T cell receptor V beta genes. J Exp Med. 1989 Jun 1;169(6):1903–1909. doi: 10.1084/jem.169.6.1903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Haqqi T. M., Banerjee S., Jones W. L., Anderson G., Behlke M. A., Loh D. Y., Luthra H. S., David C. S. Identification of T-cell receptor V beta deletion mutant mouse strain AU/ssJ (H-2q) which is resistant to collagen-induced arthritis. Immunogenetics. 1989;29(3):180–185. doi: 10.1007/BF00373643. [DOI] [PubMed] [Google Scholar]
  15. Herman A., Kappler J. W., Marrack P., Pullen A. M. Superantigens: mechanism of T-cell stimulation and role in immune responses. Annu Rev Immunol. 1991;9:745–772. doi: 10.1146/annurev.iy.09.040191.003525. [DOI] [PubMed] [Google Scholar]
  16. Holmdahl R., Klareskog L., Rubin K., Björk J., Smedegård G., Jonsson R., Andersson M. Role of T lymphocytes in murine collagen induced arthritis. Agents Actions. 1986 Dec;19(5-6):295–305. doi: 10.1007/BF01971231. [DOI] [PubMed] [Google Scholar]
  17. Holmdahl R., Klareskog L., Rubin K., Larsson E., Wigzell H. T lymphocytes in collagen II-induced arthritis in mice. Characterization of arthritogenic collagen II-specific T-cell lines and clones. Scand J Immunol. 1985 Sep;22(3):295–306. doi: 10.1111/j.1365-3083.1985.tb01884.x. [DOI] [PubMed] [Google Scholar]
  18. Keystone E. C., Minden M., Klock R., Poplonski L., Zalcberg J., Takadera T., Mak T. W. Structure of T cell antigen receptor beta chain in synovial fluid cells from patients with rheumatoid arthritis. Arthritis Rheum. 1988 Dec;31(12):1555–1557. doi: 10.1002/art.1780311213. [DOI] [PubMed] [Google Scholar]
  19. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  20. MacDonald H. R., Glasebrook A. L., Schneider R., Lees R. K., Pircher H., Pedrazzini T., Kanagawa O., Nicolas J. F., Howe R. C., Zinkernagel R. M. T-cell reactivity and tolerance to Mlsa-encoded antigens. Immunol Rev. 1989 Feb;107:89–108. doi: 10.1111/j.1600-065x.1989.tb00004.x. [DOI] [PubMed] [Google Scholar]
  21. Miller E. J. Structural studies on cartilage collagen employing limited cleavage and solubilization with pepsin. Biochemistry. 1972 Dec 19;11(26):4903–4909. doi: 10.1021/bi00776a005. [DOI] [PubMed] [Google Scholar]
  22. Miltenburg A. M., van Laar J. M., Daha M. R., de Vries R. R., van den Elsen P. J., Breedveld F. C. Dominant T-cell receptor beta-chain gene rearrangements indicate clonal expansion in the rheumatoid joint. Scand J Immunol. 1990 Jan;31(1):121–126. doi: 10.1111/j.1365-3083.1990.tb02750.x. [DOI] [PubMed] [Google Scholar]
  23. Paliard X., West S. G., Lafferty J. A., Clements J. R., Kappler J. W., Marrack P., Kotzin B. L. Evidence for the effects of a superantigen in rheumatoid arthritis. Science. 1991 Jul 19;253(5017):325–329. doi: 10.1126/science.1857971. [DOI] [PubMed] [Google Scholar]
  24. Pullen A. M., Marrack P., Kappler J. W. The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature. 1988 Oct 27;335(6193):796–801. doi: 10.1038/335796a0. [DOI] [PubMed] [Google Scholar]
  25. Savill C. M., Delves P. J., Kioussis D., Walker P., Lydyard P. M., Colaco B., Shipley M., Roitt I. M. A minority of patients with rheumatoid arthritis show a dominant rearrangement of T-cell receptor beta chain genes in synovial lymphocytes. Scand J Immunol. 1987 Jun;25(6):629–635. doi: 10.1111/j.1365-3083.1987.tb01089.x. [DOI] [PubMed] [Google Scholar]
  26. Seki N., Sudo Y., Yoshioka T., Sugihara S., Fujitsu T., Sakuma S., Ogawa T., Hamaoka T., Senoh H., Fujiwara H. Type II collagen-induced murine arthritis. I. Induction and perpetuation of arthritis require synergy between humoral and cell-mediated immunity. J Immunol. 1988 Mar 1;140(5):1477–1484. [PubMed] [Google Scholar]
  27. Seyer J. M., Hasty K. A., Kang A. H. Covalent structure of collagen. Amino acid sequence of an arthritogenic cyanogen bromide peptide from type II collagen of bovine cartilage. Eur J Biochem. 1989 Apr 15;181(1):159–173. doi: 10.1111/j.1432-1033.1989.tb14707.x. [DOI] [PubMed] [Google Scholar]
  28. Sottini A., Imberti L., Gorla R., Cattaneo R., Primi D. Restricted expression of T cell receptor V beta but not V alpha genes in rheumatoid arthritis. Eur J Immunol. 1991 Feb;21(2):461–466. doi: 10.1002/eji.1830210231. [DOI] [PubMed] [Google Scholar]
  29. Stamenkovic I., Stegagno M., Wright K. A., Krane S. M., Amento E. P., Colvin R. B., Duquesnoy R. J., Kurnick J. T. Clonal dominance among T-lymphocyte infiltrates in arthritis. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1179–1183. doi: 10.1073/pnas.85.4.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Terato K., Hasty K. A., Cremer M. A., Stuart J. M., Townes A. S., Kang A. H. Collagen-induced arthritis in mice. Localization of an arthritogenic determinant to a fragment of the type II collagen molecule. J Exp Med. 1985 Aug 1;162(2):637–646. doi: 10.1084/jem.162.2.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Trentham D. E., Townes A. S., Kang A. H. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 1977 Sep 1;146(3):857–868. doi: 10.1084/jem.146.3.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Uematsu Y. Preferential association of alpha and beta chains of the T cell antigen receptor. Eur J Immunol. 1992 Feb;22(2):603–606. doi: 10.1002/eji.1830220247. [DOI] [PubMed] [Google Scholar]
  33. Uematsu Y., Ryser S., Dembić Z., Borgulya P., Krimpenfort P., Berns A., von Boehmer H., Steinmetz M. In transgenic mice the introduced functional T cell receptor beta gene prevents expression of endogenous beta genes. Cell. 1988 Mar 25;52(6):831–841. doi: 10.1016/0092-8674(88)90425-4. [DOI] [PubMed] [Google Scholar]
  34. Uematsu Y., Wege H., Straus A., Ott M., Bannwarth W., Lanchbury J., Panayi G., Steinmetz M. The T-cell-receptor repertoire in the synovial fluid of a patient with rheumatoid arthritis is polyclonal. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8534–8538. doi: 10.1073/pnas.88.19.8534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Watson W. C., Townes A. S. Genetic susceptibility to murine collagen II autoimmune arthritis. Proposed relationship to the IgG2 autoantibody subclass response, complement C5, major histocompatibility complex (MHC) and non-MHC loci. J Exp Med. 1985 Dec 1;162(6):1878–1891. doi: 10.1084/jem.162.6.1878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. White J., Blackman M., Bill J., Kappler J., Marrack P., Gold D. P., Born W. Two better cell lines for making hybridomas expressing specific T cell receptors. J Immunol. 1989 Sep 15;143(6):1822–1825. [PubMed] [Google Scholar]
  37. Wooley P. H., Luthra H. S., Griffiths M. M., Stuart J. M., Huse A., David C. S. Type II collagen-induced arthritis in mice. IV. Variations in immunogenetic regulation provide evidence for multiple arthritogenic epitopes on the collagen molecule. J Immunol. 1985 Oct;135(4):2443–2451. [PubMed] [Google Scholar]
  38. Wooley P. H., Luthra H. S., Stuart J. M., David C. S. Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates. J Exp Med. 1981 Sep 1;154(3):688–700. doi: 10.1084/jem.154.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]

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