NEUROMUSCLUAR IMMUNOPATHOLOGY IN EAMG-RESISTANT RATS

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Gravis (EAMG), immunological differences between helper T cells from two inbred rat strains that explain disease susceptibility on the one hand (in Lewis rats) and disease-resistance on the other hand (in Wistar Furth rats). The working hypothesis for these studies is that the T cell compartment in Wistar Furth rats may lack the ability to activate responsiveness by existing B cells that have the potential to produce disease-causing antibodies; this quality may be related to a lack of T cell reactivity toward an epitope(s) contained within the AChR alpha subunit sequence alpha 100-116 that demonstrates immunodominance in Lewis rats. Studies will include an evaluation of effects on antibody-mediated inducible neuromuscular dysfunction by the elimination of this T cell reactivity in Lewis rats by neonatal tolerance induction and peptide blocking strategies. Proposed studies will also evaluate the importance of this deficit in the Wistar Furth T cell specificity repertoire by comparing the frequency of alpha 100-116 responding cells to the frequency observed in the Lewis response; included in this evaluation will be tests for the ability of WF antigen presenting cells to bind and present the alpha 100-116 peptide that may be responsible for the inability of Wistar Furth T cells to drive an anti-AChR antibody response with disease-causing potential.