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Possible Linkage of Myasthenia Gravis Susceptibility in R111 S/J Mice to a Genomic Deletion of T Cell Receptor Vβ Genes

  • Mohan Shenoy
  • Bo Wu
  • Rashmi Kaul
  • Elzbieta Goluszko
  • Chella David
  • Premkumar Christadoss
Conference paper
Part of the NATO ASI Series book series (volume 80)

Abstract

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.

Keywords

Genomic 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.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • Mohan Shenoy
    • 1
  • Bo Wu
    • 1
  • Rashmi Kaul
    • 1
  • Elzbieta Goluszko
    • 1
  • Chella David
    • 2
  • Premkumar Christadoss
    • 1
  1. 1.The Department of MicrobiologyUniversity of Texas Medical BranchGalvestonUSA
  2. 2.Department of ImmunologyMayo ClinicRochesterUSA

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