Influence of T cell specificity on the heterogeneity and disease-causing capability of antibody against the acetylcholine receptor.
Adoptive secondary anti-acetylcholine receptor (AChR) antibody responses were examined in rats to evaluate the influence of helper T cell specificity on the nature and disease-causing potential of antibody produced. Mixtures of B cells reactive with the intact AChR plus T cells reactive with purified AChR subunits (alpha, beta, gamma, delta) were transferred and antigen-challenged in immunologically naive recipient rats; the serum anti-AChR antibody produced was assessed by radioimmunoassay for differences in titers and by isoelectric focusing for differences in clonal heterogeneity as a function of the subunit specificity of T cells transferred. In addition, rats receiving different sources of AChR or AChR subunit-reactive T cells were examined for AChR-dependent muscle dysfunction. The results indicated a clear reduction in anti-AChR antibody concentrations and clonal heterogeneity in recipient rats receiving T cells of specificities restricted to individual subunits. However, except for a clear relationship between serum anti-AChR antibody concentration and disease induction, no particular AChR subunit-reactive helper T cell specificity appeared to preferentially cause muscle dysfunction. We conclude that if such relationships exists, T cells with specificities more restricted than those described here will have to be used.
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D005260:Female; D007116:Immunization, Passive; D007525:Isoelectric Focusing; D008198:Lymph Nodes / Q000276:immunology; D009119:Muscle Contraction; D009157:Myasthenia Gravis / Q000209:etiology; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000032:analysis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D001323:Autoantibodies; D011950:Receptors, Cholinergic