Immune response to the p-azobenzenearsonate (ABA)-GAT conjugate. II. Hapten-specific T cells induced with ABA-GAT in GAT responder X nonresponder F1 hybrids are restricted to the nonresponder haplotype.
Immunization of mice with the ABA-GAT conjugate stimulates GAT-specific T helper cells in GAT-responder animals and ABA-specific helpers in nonresponders. Unexpectedly, immunization of (responder X nonresponder) F1 mice, which have the GAT-responder phenotype, leads to the recruitment of both ABA- and GAT-specific clones of T helper lymphocytes. The GAT-reactive population is restricted to the haplotype of the responder parent (Iak), whereas ABA-specific T cells are mostly restricted to the nonresponder one (Ias). This is demonstrated by the ability of monoclonal antibodies to parental la antigens to inhibit T cell proliferation to GAT or ABA-Tyr in vitro. Consistently, ABA-GAT-primed F1 T cells can only activate nonresponder B cells to proliferate in the presence of ABA-Tyr and responder B lymphocytes in the presence of GAT. Furthermore, F1 T cells seem to recognize both ABA and GAT epitopes only in association with molecules encoded by the I-A subregion. Analysis of ABA-specific F1 T cell lines generated by in vitro stimulation with ABA-Tyr or ABA-GAT demonstrates a competition between GAT- and ABA-specific T cells present in the hybrid T cell repertoire and restricted to the same parental I-Ak molecule. The results indicate that F1 macrophages can present both ABA and GAT epitopes to T cells in association with the two parental and hybrid Ia determinants. It seems unlikely that the absence of GAT-specific T cells restricted to the nonresponder I-A in the F1 is due to suppressor T cells. Thus, the competition model that we propose, to explain the selective F1 T cell response to ABA-GAT, leads us to believe that GAT nonresponder animals may lack clones capable of recognizing, with a high affinity, I-As + GAT.
D000818:Animals; D001391:Azo Compounds / Q000276:immunology*; D001667:Binding, Competitive; D003433:Crosses, Genetic; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000235:genetics; D005260:Female; D005802:Genes, MHC Class II; D006238:Haploidy; D006241:Haptens / Q000235:genetics / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011108:Polymers; D013601:T-Lymphocytes / Q000276:immunology*; D010132:p-Azobenzenearsonate / Q000235:genetics / Q000276:immunology*
D001391:Azo Compounds; D000939:Epitopes; D006241:Haptens; D007130:Immunoglobulin Idiotypes; D010455:Peptides; D011108:Polymers; C022204:anti-GAT antibodies, idiotypic; C020749:GAT; D010132:p-Azobenzenearsonate