02255nas a2200385 4500000000100000008004100001260001300042653002400055653001200079653002700091653002400118653002300142653002700165653001700192653003100209653001100240653001700251653002200268653001200290653002600302653002800328653002500356653001300381653003200394653001800426100001300444700001500457700001300472700001600485245010000501300001000601490000700611520123700618022001401855 1999 d c1999 Jun10aAmino Acid Sequence10aAnimals10aAntibodies, Monoclonal10aAntigens, Bacterial10aBacterial Proteins10aEpitopes, T-Lymphocyte10aHLA Antigens10aHistocompatibility Testing10aHumans10aImmunization10aImmunophenotyping10aleprosy10aLymphocyte Activation10aMolecular Sequence Data10aMycobacterium leprae10aPeptides10aRecombinant Fusion Proteins10aT-Lymphocytes1 aOftung F1 aLundin K E1 aMeloen R1 aMustafa A S00aHuman T cell recognition of the Mycobacterium leprae LSR antigen: epitopes and HLA restriction. a151-90 v243 a
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 healthy subjects immunized with heat killed M. leprae were used as donors to establish antigen reactive CD4+ T cell lines which were screened for proliferative responses against overlapping synthetic peptides covering the C-terminal part of the antigen sequence. By using this approach we were able to identify 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 DRw53. In contrast, peptide 6 was presented to T cells only in the context of HLA-DR5 molecules. In conclusion, the M. leprae LSR protein antigen can be 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 develop leprosy. The results obtained are in support of using the LSR antigen in subunit vaccine design.
a0928-8244