T Cell Receptor Expression and Differential Proliferative Responses by T Cells Specific to a Myasthenogenic Peptide

Myasthenia gravis (MG) is a T-cell-regulated autoimmune disease in which a pathological autoantibody response is mounted against the nicotinic acetylcholine receptor of the neuromuscular junction. Our laboratory previously identified a T cell epitope, p195–212, derived from the human acetylcholine receptor α subunit, which triggered PBL to proliferate from about 70% of MG patients tested. p195–212 was also found to be an immunodominant T cell epitope in SJL mice and a cryptic epitope in C3H.SW mice. Inoculation of naive SJL mice with cells from a p195–212-specific syngeneic T cell line caused MG-related autoimmune manifestations in those mice. In these studies we analyzed TCR α and β chain sequences used by T cell lines and clones from both high- and low-responder mouse strains in response to p195–212. T cell lines generated from either strain expressed single TCR Vβ gene segments (Vβ17 in SJL mice and Vβ8 in C3H.SW mice). By deleting Vβ17-expressing T cells in p195–212-immunized SJL mice we established a T cell line that expressed the Vβ6 gene product, suggesting that SJL mice are not limited to using a single Vβ gene segment in response to p195–212. In addition, we found that N- and/or C-terminal-truncated peptides of p195–212, presented under the same culture conditions to different clones bearing the same TCR αβ chain, could elicit very different proliferative responses from the clones. Thus, even within a constrained system, factors other than TCR sequence contribute to the differential stimulation of T cell responses.