Human T cell recognition of the Mycobacterium leprae LSR antigen: epitopesand HLA restriction

We have in this work mapped epitopes and HLA molecules used in human T cell recognition of the Mycobacterium leprae LSR protein antigen. HLA typed hea lthy subjects immunized with heat killed M. leprae were used as donors to e stablish antigen reactive CD4+ T cell lines which were screened for prolife rative responses against overlapping synthetic peptides covering the C-term inal part of the antigen sequence. By using this approach we were able to i dentify two epitope regions represented by peptide 2 (aa 29-40) and peptide 6 (aa 49-60), of which the former was mapped in detail by defining the N- and C-terminal amino acid positions necessary for T cell recognition of the core epitope, MHC restriction analysis showed that peptide 2 was presented to T cells by allogeneic cells coexpressing HLA-DR4 and DRw53 or DR7 and D Rw53. In contrast; peptide 6 was presented to T cells only in the context o f HLA-DR5 molecules. In conclusion, the M. leprae LSR protein antigen can b e recognized by human T cells in the context of multiple HLA-DR molecules, of which none are reported to be associated with the susceptibility to deve lop leprosy. The results obtained are in support of using the LSR antigen i n subunit vaccine design, (C) 1999 Federation of European Microbiological S ocieties. Published by Elsevier Science B.V. All rights reserved.