PROMISCUOUS T-CELL RECOGNITION OF AN H-2 IA-PRESENTED MYCOBACTERIAL EPITOPE

Genetically permissive T cell epitopes are an important prerequisite f or the development of peptide-based vaccines or immunodiagnostic reage nts. We have investigated the structural requirements of permissive T cell recognition of peptide p350-369 from the 38-kDa antigen of Mycoba cterium tuberculosis. This peptide was found to be immunogenic in mice of the H-2(b, bm12, d, s and k), but not of the H-2(f) genotype. T ce ll responses were restricted by I-A class II molecules. The same epito pe core was recognized in the H-2(b, d and k) genotypes. T cell hybrid s from BALB/c and C57BL/10 mice were used to determine: (i) the critic al residues using substituted peptide derivatives and (ii) the degree of T cell promiscuity. Two out of five BALB/c (H-2(d))-derived hybrido mas tested displayed promiscuous peptide recognition in the context of H-2(b) and H-2(bm12) antigen-presenting cells. The recognition of cri tical residues was found to be uniform for all five hybridomas when te sted with syngeneic antigen-presenting cells; additional critical resi dues were identified when the peptide was recognized in the context of allogeneic antigen-presenting cells. Only one of the four tested C57B L/10 (H-2(b)) hybridomas showed promiscuity in the context of H-2(bm12 ). Each of these C57BL/10-derived clones had a distinct response profi le toward the critical residues. We propose that the demonstrated T ce ll promiscuity involves peptide interaction with polymorphic H-2 I-A r esidues.