Antigen presentation and T cell specificity repertoire in determining responsiveness to an epitope important in experimental autoimmune myasthenia gravis

The overall goal of this study was to define, in experimental autoimmune myasthenia 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 was 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 a determinant(s) associated with the alpha subunit sequence α100-116 of the acetylcholine receptor (AChR) that demonstrates immunodominance in Lewis rats. Results presented below are consistent with the conclusion that there is a deficit in the Wistar Furth (WF) T cell specificity repertoire responsible for unresponsiveness to this important AChR epitope; this deficit exists despite the apparent ability of WF antigen presenting cells to bind and present the α100-116 peptide, and is likely responsible for the inability of Wistar Furth T cells to drive an anti-AChR antibody response with disease-causing potential.