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 whi ch a pathological autoantibody response is mounted against the nicotin ic acetylcholine receptor of the neuromuscular junction. Our laborator y previously identified a T cell epitope, p195-212, derived from the h uman acetylcholine receptor alpha subunit, which triggered PEL to prol iferate 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 epito pe in C3H.SW mice. Inoculation of naive SJL mice with cells from a p19 5-212-specific syngeneic T cell line caused MG-related autoimmune mani festations in those mice. In these studies we analyzed TCR alpha and b eta chain sequences used by T cell lines and clones from both high- an d low-responder mouse strains in response to p195-212. T cell lines ge nerated from either strain expressed single TCR V beta gene segments ( V beta 17 in SJL mice and V beta 8 in C3H.SW mice). By deleting V beta 17-expressing T cells in p195-212-immunized SJL mice we established a T cell line that expressed the V beta 6 gene product, suggesting that SJL mice are not limited to using a single V beta gene segment in res ponse to p195-212. In addition, we found that N- and/ or C-terminal-tr uncated peptides of p195-212, presented under the same culture conditi ons to different clones bearing the same TCR alpha beta chain, could e licit very different proliferative responses from the clones. Thus, ev en within a constrained system, factors other than TCR sequence contri bute to the differential stimulation of T cell responses. (C) 1997 Aca demic Press.