Possible Linkage of Myasthenia Gravis Susceptibility in R111 S/J Mice to a Genomic Deletion of T Cell Receptor Vβ Genes
Part of the
NATO ASI Series
book series (volume 80)
Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigue. The defective neuromuscular transmission in MG is due to a functional loss of the nicotinic acetylcholine receptor (AChR) in the postsynaptic membrane, which is the result of the effects of anti-AChR antibodies and complement (Lindstrom et al, 1988). Many caucasian MG patients possess HLA-B8, and those having a subtype of the DR3 haplotype polymorphic at the DQβ locus, run the greatest risk of developing MG (Bell, et al, 1986). Moreover, HLA-DR3-restricted, AChR-specific T cell lines were generated from a patient with MG (Bell, et al, 1986). Experimental autoimmune myasthenia gravis (EAMG) susceptibility has also been linked to MHC genes (Christadoss, 1989; Christadoss and Shenoy, 1992). A gene conversion event between the immune response genes Eβb and Aβb in the B6.CH-2bml2 (bml2) strain, which altered three amino acids (Ile-67 to Phe; Arg-70 to Gln; Thr-71 to Lys) of the Aβ chain, suppressed EAMG development (Christadoss et al, 1985), and thus, the Aβ chain was implicated in the pathogenesis. Further, the immune response to AChR could be suppressed by in vivo administration of anti-IA antibodies (Waldor et al, 1983). EAMG in mice can either be prevented, or clinical remission induced, by in vivo administration of monoclonal antibodies (mAb) to CD4 (Christadoss and Dauphinee, 1986), suggesting a requirement for CD4+ helper T cells in the production of pathogenic anti-AChR antibodies by B cells.
KeywordsGenomic Deletion Immune Response Gene Congenic Mouse Gene Conversion Event Experimental Autoimmune Myasthenia
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Banerjee S., Haqqui T.M., Luthra H.S., Stuart J.M. and David C.S. (1988). Possible role of Vp T cell receptor genes in susceptibility to collagen induced arthritis in mice. J Exp Med
167, 832–839.PubMedCrossRefGoogle Scholar
Beall S.S., Concannon P., Biddison W.A., McFarland H., Hood L., and McFarlin D.E. (1987). Analysis of germline Vα and Vβ genes in patients with multiple sclerosis. J Cell Biochem
11D, 223.Google Scholar
Behlke M.A., Hubert J.S., Huqqi K. and Loh D.Y. (1986). Murine TCR mutants with deletions of p-chain variable region genes. Proc Natl Acad Sci (USA)
83, 767–771.CrossRefGoogle Scholar
Bell J., Smoot S., Newley C., Toyka K., Rassenti L., Smith D., Hohlfeld R., McDevitt H., and Steinman L. (1986). HLA-DQ beta-chain polymorphism linked to MG. Lancet
Christadoss P, and Dauphinee M.J. (1986). Immunotherapy for myasthenia gravis: A murine model. J. Immunol.
136, 2437–2440.PubMedGoogle Scholar
Christadoss P, Lindstrom J.M., Melvold R.W. and Talal N. (1985). Mutation at I-Aβ chain prevents experimental autoimmune myasthenia gravis. Immunogenetics
21, 33–38.PubMedCrossRefGoogle Scholar
Christadoss P., Lindstrom J., Munro S. and Talal N. (1985). Muscle acetylcholine receptor loss in murine experimental autoimmune MG: Correlated with cellular, humoral and clinical responses. J. Neuroimmunol.
8, 29–34.PubMedCrossRefGoogle Scholar
Christadoss P., Shenoy M. (1992). Molecular immunopathogenesis of experimental autoimmune myasthenia gravis. Regional Immunol
. 4, 314–320.Google Scholar
Christadoss P., Lindstrom J.M., Talal N., Duvic C.R., Kalantri A. and Shenoy M. (1986). Immune response gene control of lymphocyte proliferation induced by acetylcholine receptor specific helper factor derived from lymphocytes of myasthenic mice. J. Immunol.
137, 1845–1849.PubMedGoogle Scholar
Demaine A.G., Millward B.A., Vaughan R.W. and Welsh K.I. (1987). T cell receptor beta chain gene polymorphisms are associated with certain autoimmune diseases. J Cell Biochem. 11D, 255. 0Google Scholar
Demaine A.G., Vaughan R.W., Taube D.H. and Welsh K.I. (1988). Association of membranous nephropathy with T cell receptor constant p chain and Ig heavy chain with region polymorphisms. Immunogenetics
27, 19–23.PubMedCrossRefGoogle Scholar
Haqqi T., Banerjee S., Anderson G.D. and David C.S. (1989). An inbred mouse strain with a massive deletion of T cell receptor Vp genes.J Exp Med
169, 1903–1909.PubMedCrossRefGoogle Scholar
Hohlfeld R., Conti-Tronconi B., Kalies I., Bertrams Jr. and Toyka K.V. (1985). Genetic restriction of autoreactive acetylcholine receptor specific T lymphocytes in myasthenia gravis. J. Immunol.
135, 2393–2399.PubMedGoogle Scholar
Hoover M.L., Angelini G., Ball E., Stastny P., Marks J., Rosenstock J., Raskin P., Ferrara G.B., Tosi R. and Capra J.D. (1986). HLA-DQ and T cell receptor genes in insulin-dependent diabetes mellitus. Cold Spring Harbor Symp, Quant Biol
51, 803–809.Google Scholar
Lindstrom, J., Shelton, D. and Fujii, Y. (1988). Myasthenia gravis. Adv. Immunol.
42, 233–284.PubMedCrossRefGoogle Scholar
Lindstrom J.M., Einarson B.L. and Tzartos S. (1981). Production and assay of antibodies to acetylcholine receptor. Methods Enzymol
74, 432–460.PubMedCrossRefGoogle Scholar
Rodriguez, M., Patrick, A.K., Peese, L.R. and David, C.S. (1992). Role of T cell receptor Vp genes in Theiler’s virus-induced demyelination of mice. J Immunol
. 148, 921–927.PubMedGoogle Scholar
Shenoy, M., Oshima, M., Atassi, M.Z. and Christadoss, P. (1993). Suppression of experimental autoimmune myasthenia gravis by epitope-specific neonatal tolerance to synthetic region α146–162 of acetylcholine receptor. Clinic. Immunol. Immunopath.
66, 230–238.CrossRefGoogle Scholar
Urban J, Kumar V., Kono D.H., Gomez C., Horvath S.J., Clayton J., Ando D.G., Sercarz E.E. and Hood L. (1988). Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell
54, 577–592.PubMedCrossRefGoogle Scholar
Waldor M.K., Sriram S., McDevitt H.D., Steinman L. (1983) In vivo therapy with monoclonal anti-la antibody suppresses immune response to acetylcholine receptor. Pro. Natl. Acad. Sci. USA.
80: 2713–2717.CrossRefGoogle Scholar
Weetman A.P., So A.K., Roe C., Walport M.J. and Foroni L. (1987). T cell receptor Vp chain polymorphism linked to primary autoimmune hypothyroidism but not Graves disease. Hum Immunol
20, 167–173.PubMedCrossRefGoogle Scholar
Zamvil S., Mitchell D.J., Lee N.E., Moore A.C., Waldor M.K., Sakai K., Rothbard J.B., McDevit HO, Steinman L. and Acha-Orbea H. (1988). Predominant expression of a T cell receptor Vp gene subfamily in autoimmune encephalomyelitis. J Exp Med
167, 1586–1596.PubMedCrossRefGoogle Scholar
© Springer-Verlag Berlin Heidelberg 1994