Primary structure and MHC restriction of peptide-defined T cell epitopes from recombinant mycobacterial protein antigens

ABSTRACT

By combining DNA subclone and synthetic peptide approaches, immunogenic epitopes have been mapped from the mycobacterial heat shock proteins [HSP] of 18. 65 and 70 kD, as well as from a novel non-HSP antigen kD recognized by antigen-specific human T cells. In addition the HLA-DR molecules used in antigen presentation of the individual peptide-defined epitopes have been identified. The doner groups used for establishing antigen-specific CD4+ T cell clones and lines were primarily healthy subjects immunized with Mycobacterium bovis BCG and killed Mycobacterium leprae. The results showed that HSP18 contains on epitope [aa 38-50] presented by HLA-DR4; HSP65 contains 4 epitopes presented by DR1 and DR2 and 5 epitopes presented by DR2, DR3, DR5, DR7, and DRw53. The 24-kD non-HSP antigen also displayed one HLA-DRw53-restricted T cell epitopes. In conclusion, the individual HSP T cell epitopes defined here are exclusively presented by only one HLA-DR molecule. However, at the protein level the results suggest that HSP65 and HSP70 are relevant to the subunit vaccine design, since they contain multiple T cell epitopes which can be presented by a spectrum of different HLA-DR molecules