Predominant recognition of species‐specific determinants of the GroES homologues from Mycobacterium leprae and M. tuberculosis

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Abstract
The Mycobacterium leprae and M. tuberculosis 10 000 MW heat‐shock protein homologues of GroES have previously been identified as major immunogens 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 recognize prominently the species‐specific determinants localized within amino acid residues 21–40 and 49–72. Analysis of the molecular determinants of species‐specificity for the M. leprae GroES sequence 25–40, using T‐cell hybridomas and major histocompatibility complex (MHC)‐binding assays, led to the identification of epitope cores and critical residues. Interestingly, closely overlapping epitope cores were found to be restricted by either H‐2Ad (24–34) or H‐2Ed (28–34). Furthermore, the site recognized by the M. leprae‐specific monoclonal antibodies 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‐shock protein despite its highly conserved amino acid sequence. This finding suggests the feasibility of identifying a sufficient number of M. leprae‐specific determinants for a composite T‐cell immunodiagnostic reagent for tuberculoid leprosy.