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Cross‐reactive epitopes and HLA‐restriction elements in human T cell recognition of the Mycobacterium leprae 18‐kD heat shock protein

We have previously demonstrated that the Mycobacterium leprae 18‐kD heat shock protein (HSP18) is represented among the antigenic targets of human T cell responses induced by M. leprae immunization and that the peptide 38–50 serves as an immunodominant epitope recognized by CD4+ T cell clones. By using peripheral blood mononuclear cells and T cell lines from the same donor group, we have in this study shown that the M. leprae HSP18 and peptide 38–50 were recognized by memory T cells 8 years after immunization with M. leprae. The finding that M. bovis BCG‐induced T cell lines responded to M. leprae HSP18, but not to the peptide 38–50, suggested the existence of additional T cell epitopes of a cross‐reactive nature. Consistent with this, testing of the T cell lines for proliferative responses to the complete HSP18 molecule, truncated HSP18 (amino acid (aa) residues 38–148) and overlapping synthetic peptides, made it possible to identify two cross‐reactive epitope regions defined by aa residues 1–38 and 41–55. While peptide 38–50‐reactive T cell clones showed limited cross‐reactivity by responding to M. leprae, M. avium and M. scrofulaceum, the T cell lines specific to the epitopes 1–38 and 41–55 were broadly cross‐reactive, as demonstrated by their response to M. leprae, M. tuberculosis complex, M. avium and other mycobacteria. MHC restriction analysis of the HSP18‐responding T cell lines showed that the epitopes 1–38 and 38–50 were presented by one of the two HLA‐DR molecules expressed from self HLA‐DRB1 genes, whereas the epitope 41–55 was recognized in the presence of autologous as well as HLA‐DR and HLA‐DQ mismatched allogeneic antigen‐presenting cells. The results obtained in this study made it possible to identify cross‐reactive T cell epitopes of the M. leprae HSP18, and provide an explanation for T cell recognition of this antigen in individuals infected with species of the M. tuberculosis complex or environmental mycobacteria.