Specificity and function of immunogenic peptides from the 35-kilodalton protein of Mycobacterium leprae

We identified a T-cell determinant of the 35-kDa antigen of Mycobacterium l eprae which is discriminatory against cross-sensitization by its closely re lated homologue in Mycobacterium avium. From synthetic peptides covering th e entire sequence, those with the highest affinity and permissive binding t o purified HLA-DR molecules were evaluated for the stimulation of prolifera tion of peripheral blood mononuclear cells (PBMCs) from leprosy patients an d healthy sensitized controls. Responses to the peptide pair 206-224, diffe ring by four residues between M. leprae and M. avium, involved both species -specific and cross-reactive T cells. Lymph node cell proliferation in HLA- DRB1*01 transgenic mice was reciprocally species specific, hut only the res ponse to the M. leprae peptide in the context of DR1 was immunodominant. Of the cytokines in human PBMC cultures, gamma interferon production was negl igible, while interleukin 10 (IL-10) responses in both patients and control s were more pronounced. IL-10 was most frequently induced by the shared 241 -255 peptide, indicating that environmental cross-sensitization may skew th e response toward a potentially pathogenic cytokine phenotype.