RECOGNITION OF PEPTIDE EPITOPES OF THE 16,000-MW ANTIGEN OF MYCOBACTERIUM-TUBERCULOSIS BY MURINE T-CELLS

The T-cell repertoire to a prominent immunogen of Mycobacterium tuberc ulosis has been investigated on the assumption that differences in epi tope specificity could influence the protective and pathogenic host re actions. Proliferative responses of lymph node and spleen cells to ove rlapping peptides, spanning the entire sequence of the 16,000 MW prote in antigen were analysed in C57BL/10 and B10.BR mice. Following footpa d priming and in vitro challenge with homologous peptide, 12 out of th e 14 peptides tested were found to be immunogenic. However, only two p eptides of residues 31-40 and 71-91 stimulated strong proliferative re sponses of T cells from mice which had been presensitized with either killed or live M. tuberculosis organisms; another three peptides were only weakly stimulatory. These epitopes have been immunodominant in bo th H-2b and H-2k mouse strains, indicating the genetically permissive nature of their recognition. Furthermore, both major immunodominant ep itopes were found to be species specific for the M. tuberculosis compl ex and therefore potentially suitable for the early diagnosis of tuber culous infection.