Antigen-presenting cells from nonresponder strain 2 guinea pigs are fully competent to present bovine insulin B chain to responder strain 13 T cells. Evidence against a determinant selection model and in favor of a clonal deletion model of immune response gene function.
To test directly the determinant selection hypothesis of immune response gene function, we primed strain 13 T lymphocytes in vitro with allogeneic bovine insulin pulsed strain 2 macrophages. Strain 2 macrophages were found to be fully competent to present bovine insulin B chain to strain 13 T cells despite the fact that strain 2 guinea pigs are normally totally unresponsive to this antigen. These results are incompatible with a strict interpretation of the determinant selection hypothesis, which would have predicted that strain 2 macrophages would have been restricted to the presentation of A chain loop determinants. In addition, a comparison of the reactivity profiles of self-Ia- and allo-Ia-restricted strain 13 T cells to a series of synthetic B chain peptide fragments revealed that the allo-Ia-restricted populations could be activated by autologous guinea pig insulin. Taken together, these observations strongly suggest that the clonal deletion of self-reactive cells is likely to be I region restricted and that nonresponsiveness to any protein antigen may result from a restriction in the T cell repertoire that is generated during ontogeny by a clonal deletion mechanism of tolerance to self.
D000818:Animals; D002417:Cattle; D002872:Chromosome Deletion; D002999:Clone Cells / Q000276:immunology; D000939:Epitopes / Q000235:genetics; D005802:Genes, MHC Class II; D006168:Guinea Pigs; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance; D007328:Insulin / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008954:Models, Biological; D010446:Peptide Fragments / Q000276:immunology; D012756:Sheep; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D010446:Peptide Fragments