I-A alpha k transgene pairs with I-A beta b gene and protects C57BL10 mice from developing autoimmune myasthenia gravis.
The I-A beta gene has been implicated in the pathogenesis of experimental autoimmune myasthenia gravis (EAMG), with amino acids at positions 67, 70, and 71 of the I-A beta b chain that play a crucial role. In addition, the cell surface expression of the I-E molecule in C57BL10.E alpha k transgenic mice was associated with the partially suppressed serum anti-acetylcholine receptor antibody and clinical expression of EAMG. In this study, the contribution of the I-A alpha gene and the A beta b:A alpha k transpair in EAMG pathogenesis is assessed. The I-A alpha k transgene was introduced into the B10 (A beta b:A alpha b) strain, and the I-A alpha k chain was paired with I-A beta b; therefore, the A beta b:A alpha k complex was expressed on the cell surface. Expression of the A beta b:A alpha k transpair in C57BL10 transgenic mice suppressed the cellular and humoral autoimmune responses to acetylcholine receptors (AChR), reduced the amount of muscle AChR bound with antibody, and significantly reduced the incidence of muscle weakness and its associated abnormal electrophysiological response.
Christadoss
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Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
David
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CS
Keve
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D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001327:Autoimmune Diseases / Q000235:genetics*; D005796:Genes; D007111:Immunity, Cellular / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009157:Myasthenia Gravis / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics
D011948:Receptors, Antigen, T-Cell