PREDOMINANT RECOGNITION OF SPECIES-SPECIFIC DETERMINANTS OF THE GROESHOMOLOGS FROM MYCOBACTERIUM-LEPRAE AND M. TUBERCULOSIS

The Mycobacterium leprae and M, tuberculosis 10000 MW heat-shock prote in homologues of GroES have previously been identified as major immuno gens for human T cells. We used synthetic peptides to characterize the determinants recognized by murine T cells. The findings suggest that, despite 90% sequence identity between these two proteins, T cells rec ognize prominently the species-specific determinants localized within amino acid residues 21-40 and 49-72. Analysis of the molecular determi nants of species-specificity for the M. leprae GroES sequence 25-40, u sing T-cell hybridomas and major histocompatibility complex (MHC)-bind ing assays, led to the identification of epitope cores and critical re sidues. Interestingly, closely overlapping epitope cores were found to be restricted by either H-2A(d) (24-34) or H-2E(d) (28-34). Furthermo re, the site recognized by the M. leprae-specific monoclonal antibodie s ML06 and ML10 was also localized in the overlapping sequences 25-31 and 25-29. In conclusion, we demonstrated that immunodominant species- specific T-and B-cell epitopes can be found in a mycobacterial heat-sh ock protein despite its highly conserved amino acid sequence. This fin ding suggests the feasibility of identifying a sufficient number of M. leprae-specific determinants for a composite T-cell immunodiagnostic reagent for tuberculoid leprosy.