HLA-class II-associated control of antigen recognition by T cells in leprosy; a prominent role for the 30/31-kDa antigens

Abstract

The recognition of 16 mycobacterial antigens (Ag) by a panel of T-cell lines from leprosy patients and healthy exposed individuals from an endemic population was examined within the context of expressed HLA-DR molecules. Although overall no significant differences were found between the frequencies of Ag recognition in the different subject groups, when Ag-specific T-cell responses were examined within the context of HLA-DR, a highly significant difference was found in the recognition of the 30/31-kDa Ag. HLA-DR3 appeared to be associated with high T-cell responsiveness to the 30/31-kDa Ag in healthy contacts (p = 0.01) but, conversely, with low T-cell responsiveness to this Ag in tuberculoid patients (p = 0.005). Within the group of HLA-DR3-positive individuals, differences in 30/31-kDa directed T-cell responsiveness were highly significant not only between healthy individuals and tuberculoid patients (p <0.0001), but also between healthy individuals and lepromatous patients (p = 0.009) and, consequently, between healthy individuals compared with leprosy patients as a group (p <0.0001). A dominant HLA-DR3-restricted epitope was recognized by healthy contacts in this population. It has been proposed that secreted Ags may dominate acquired immunity early in infection. The low T-cell response to the secreted, immunodominant 30/31-kDa Ag in HLA-DR3-positive leprosy patients in this population may result in retarded macrophage activation and delayed bacillary clearance which, in turn, may lead to an enhanced Ag load followed by T cell-mediated immunopathology.