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 alpha 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 alpha and beta 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 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 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 alpha beta 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.
Kirshner
S L
SL
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Waisman
A
A
Zisman
E
E
Ben-Nun
A
A
Mozes
E
E
D000595:Amino Acid Sequence; D000818:Animals; D002999:Clone Cells; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D011950:Receptors, Cholinergic / Q000276:immunology*; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology*
D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011950:Receptors, Cholinergic