Abstract
Collagen-induced arthritis (CIA) is a rodent arthritis model in which immunization with heterologous type II collagen induces an inflammatory polyarthritis. Susceptibility to the disease is mediated by major histocompatibility complex (MHC) genes as well as genes at other loci. Previous studies of the SWR/J mouse strain, which is resistant to CIA despite bearing the susceptible H-2 q haplotype, have suggested that this resistance is the result of a deletion of T-cell receptor (Tcr) Vb gene segments which is carried by this strain. Other studies have implicated a deficiency in complement component C5 as the cause for the resistance. In order to assess the relative importance of these two genes in susceptibility to CIA, and to provide an estimate of the number of independent genes involved in the disease, we analyzed 196 F2 progeny of a (DBA/1 × SWR/J) cross for arthritis susceptibility, and expression of both C5 and Tcr genes. Thirty of the F2 progeny developed arthritis. All of the arthritic mice had at least one copy of the wild-type C5 allele, while the Tcr-Vb haplotypes were distributed in Mendelian fashion. These results demonstrate that C5 sufficiency is an absolute requirement for CIA, but that Tcr-Vb genes located within the SWR deletion have little influence. Genetic analysis of the incidence rate suggests that there is polygenic control of susceptibility to CIA and that in addition to H-2, 5–6 other independent loci (including C5) may be involved.
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Acha-Orbea, H., Mitchell, D. J., Timmermann, L., Wraith, D. C., Tausch, G. S., Waldor, M. K., Zamvil, S. S., McDevitt, H. O., and Steinman, L.: Limited heterogeneity of T-cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell 54: 263–273, 1988
Acha-Orbea, H., Steinman, L., and McDevitt, H. O.: T-cell receptors in murine autoimmune diseases. Annu Rev Immunol 7: 371–405, 1989
Banerjee, S., Haqqi, T. M., Luthra, H. S., Stuart, J. M., and David, C. S.: Possible role of Vb T-cell recceptor genes in susceptibility to collagen-induced arthritis in mice. J Exp Med 167: 832–839, 1988
Banerjee, S., Anderson, G. D., Luthra, H. S., and David, C. S.: Influence of complement C5 and Vb T-cell receptor mutations on susceptibility to collageninduced arthritis in mice. J Immunol 142: 2237–2243, 1989
Behlke, M. A., Chou, H. S., Huppi, K., and Loh, D. Y.: Murine T-cell receptor mutations with deletions of b-chain genes. Proc Natl Acad Sci USA 83: 767–771, 1989
Chou, H. S., Nelson, C. A., Godambe, S. A., Chaplin, D. D., and Loh, D. Y.: Genomic organization of the murine T-cell receptor b-chain genes. Science 238: 545–548, 1987
Cinader, B., Dubiski, S., and Wardlaw, A. C.: Distribution, inheritance, and properties of an antigen, MUB1, and its relation to hemolytic complement. J Exp Med 120: 897–902, 1964
Cremer, M. A.: Collagen-induced arthritis in rats. In R. A. Greenwald and H. S. Diamond (eds.): Handbook of Animal Models for the Rheumatic Diseases, Vol 1, pp. 17–37, CRC Press, Boca Raton, FL, 1988
Erikson, R. P., Tachibana, D. K., Herzenberg, L. A., and Rosenberg, L. T.: A single gene controlling hemolytic complement and a serum antigen in the mouse. J Immunol 92: 611–616, 1964
Griffiths, M. M., Eichwald, R. J., Martin, J. H., Smith, C. B., and DeWitt, C. W.: Immunogenetic control of experimental type II collagen induced arthritis. I. Susceptibility and resistance among inbred strains of rats. Arthritis Rheum 24: 781–789, 1981
Haqqi, T. M., Banerjee, S., Jones, W. L., Anderson, G., Behlke, M. A., Loh, D. Y., Luthra, H. S., and David, C. S.: Identification of T-cell receptor Vb deletion mutant mouse strain AU/ssJ (H-2q) which is resistant to collageninduced arthritis. Immunogenetics 29: 180–185, 1989
Holmdahl, R., Klareskog, L., Rubin, K., Larrson, E., and Wigzell, H.: T-cells in collagen-induced arthritis in mice: Characterization of arthritogenic collagen II specific T-lymphocyte lines and clones that can transfer arthritis. Scand J Immunol 22: 295–301, 1986
Klotz, J. L., Barth, R. K., Kiser, G. L., Hood, L. E., and Kronenberg, M.: Restriction fragment length polymorphisms of the mouse T-cell receptor gene families. Immunogenetics 29: 191–201, 1989
Kumar, V., Kono, D. H., Urban, J. L., and Hood, L. E.: The T-cell receptor repertoire and autoim,une diseases. Annu Rev Immunol 7: 657–682, 1989
Luthra, H. S., Wooley, P. H., Dillon, A. M., Singh, S. K., Lafuse, W. P., Krco, C. J., Huse, A., Stuart, J. M., Griffiths, M. M., and David, C. S.: Immunogenetics of collagen-induced arthritis (CIA) in mice. A model of autoimmune disease. Ann NY Acad Sci 475: 361–363, 1986
Reife, R. A., Loutro, N., Watson, W. C., Hasty, K. A., and Stuart, J. M.: SWR mice are resistant to collagen-induced arthritis but produce potential arthritogenic antibodies. Arthritis Rheum, in press, 1991
Smith, L. R., Plaza, A., Singer, P. A., and Theofilopoulos, A. N.: Coding sequence polymorphisms among Vb T-cell receptor genes. J Immunol 144: 3234–3237, 1990
Spinella, D. G.: A rapid method for genotyping mice for T-cell receptor Vβa and Vβb haplotypes by PCR analysis of whole blood. J Immunol Methods 235: 209–212, 1990
Staerz, U. D., Rammensee, H.-G., Bendetto, J. D., and Bevan, M. J.: Characterization of a murine monoclonal antibody specific for an allotypic determinant on T-cell antigen receptor. J Immunol 134: 3994–4000, 1985
Stuart, J. M., Cremer, M. A., Townes, A. S., and Kang, A. H.: Type II collagen-induced arthritis in rats: Passive transfer with serum and evidence that IgG anticollagen antibodies can cause arthritis. J Exp Med 155: 1–16, 1982
Stuart, J. M., Tomoda, K., Townes, A. S., Yoo, T. J., and Kang, A. H.: Serum transfer of collagen-induced arthritis. II. Identification and localization of autoantibody to type II collagen in donor ad recipient rats. Arthritis Rheum 26: 1237–1244, 1983
Stuart, J. M., Townes, A. S., and Kang, A. H.: Collagen autoimmune arthritis. Annu Rev Immunol 2: 199–218, 1984
Trentham, D. E., Dynesius, R. A., and David, J. R.: Passive transfer by cells of collagen induced arthritis in rats. J Clin Invest 62: 359–366, 1978
Urban, J. L., Kumar, V., Kono, D. H., Gomez, C., Horvath, S. J., Clayton, J., Ando, D. G., Sercarz, E. E., and Hood, L. E.: Restricted usage of T-cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell 54: 577–592, 1988
Watson, W. C. and 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 162 : 1878–1891, 1985
Watson, W. C., Brown, P. S., Pitcock, J. A., and Townes, A. S.: Passive transfer studies with type II collagen antibody in B10.D2/old and new line and C57BL/6 normal and beige (Chediak-Higadi) strains: evidence of important roles for C5 and multiple inflammatory cell types in the development of erosive arthritis. Arthritis Rheum 30: 460–465, 1987
Wooley, P. H., Luthra, H. S., Stuart, J. M., and David, C. S.: Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I-region) linkage and antibody correlates. J Exp Med 154: 688–700, 1981
Wooley, P. H., Dillon, A. M., Luthra, H. S., Stuart, J. M., and David, C. S.: Genetic control of type II collagen-induced arthritis in mice: Factors influencing disease susceptibility and evidence for multiple MHC-associated gene control. Transplant Proc 15: 180–187, 1983
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Spinella, D.G., Jeffers, J.R., Reife, R.A. et al. The role of C5 and T-cell receptor Vb genes in susceptibility to collagen-induced arthritis. Immunogenetics 34, 23–27 (1991). https://doi.org/10.1007/BF00212308
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DOI: https://doi.org/10.1007/BF00212308