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

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Author: Thole, J.E.R. · Janson, A.A.M. · Cornelisse, Y. · Schreuder, G.M.T. · Wieles, B. · Naafs, B. · Vries, R.R.P. de · Ottenhoff, T.H.M.
Type:article
Date:1999
Institution: Gaubius instituut TNO
Source:Journal of Immunology, 11, 162, 6912-6918
Identifier: 235044
Keywords: Biology · Epitope · HLA antigen class 2 · HLA DP antigen · Mycobacterium antigen · Antigen recognition · Antigen specificity · Cell line · Cellular immunity · Controlled study · Human cell · Lepromatous leprosy · Leprosy · Macrophage activation · Major clinical study · Tuberculoid leprosy · Antigens, Bacterial · Epitope Mapping · Epitopes, T-Lymphocyte · HLA-DR Antigens · HLA-DR3 Antigen · Humans · Immunophenotyping · Leprosy · Lymphocyte Activation · Molecular Weight · Mycobacterium leprae · T-Lymphocytes

Abstract

The recognition of 16 mycobacterial Ags 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 enhanced Ag load followed by T cell-mediated immunopathology. Chemicals/CAS: Antigens, Bacterial; Epitopes, T-Lymphocyte; HLA-DR Antigens; HLA-DR3 Antigen