T cells reactive with a small synthetic peptide of the acetylcholine receptor can provide help for a clonotypically heterogeneous antibody response and subsequently impaired muscle function.
The influence of T cell specificity was evaluated with regard to its role in the antibody response against the acetylcholine receptor (AChR) and resulting AChR-dependent muscle dysfunction. The reactivity of immune Th cells was restricted to a small region of the AChR alpha-subunit (amino acid residues 100-116) reported to be highly immunogenic. T cells primed to this peptide were found to demonstrate significant proliferation when challenged in vitro with either the homologous peptide or the intact AChR. Adoptive transfer of the peptide-immune T cells into immunologically naive recipient rats followed by AChR challenge resulted in the production of anti-AChR antibodies very similar to those produced under the regulation of T cells immune to the entire intact AChR with regard to overall clonotypic heterogeneity (measured by IEF) and their ability to interfere with AChR-dependent muscle contraction. Interestingly, when the threonine at position 106 was substituted with a proline, the resulting peptide continued to be equally, if not exceedingly, capable of stimulating T cell-proliferative responses, but was found to be ineffective at stimulating the levels of anti-AChR antibodies necessary for producing neuromuscular dysfunction.
Yeh
T M
TM
Department of Microbiology, University of Texas Health Science Center, San Antonio 78284.
Krolick
K A
KA
D000818:Animals; D000917:Antibody Formation; D003472:Curare / Q000494:pharmacology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D009469:Neuromuscular Junction / Q000502:physiology*; D010455:Peptides / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011978:Receptors, Nicotinic / Q000276:immunology*; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D010455:Peptides; D011978:Receptors, Nicotinic; D003472:Curare