Human T cell recognition of the Mycobacterium leprae LSR antigen: epitopes and 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 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.
Oftung
F
F
Department of Vaccinology, National Institute of Public Health, Oslo, Norway. frederik.oftung@folkehelsa.no
Lundin
K E
KE
Meloen
R
R
Mustafa
A S
AS
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007114:Immunization; D016130:Immunophenotyping; D007918:Leprosy / Q000517:prevention & control; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; C084997:LSR2 protein, Mycobacterium leprae; D010455:Peptides; D011993:Recombinant Fusion Proteins