Title
HLA-class II-associated control of antigen recognition by T cells in leprosy: A prominent role for the 30/31-kDa antigens
Author
Thole, J.E.R.
Janson, A.A.M.
Cornelisse, Y.
Schreuder, G.M.T.
Wieles, B.
Naafs, B.
de Vries, R.R.P.
Ottenhoff, T.H.M.
Gaubius instituut TNO
Publication year
1999
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
Subject
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
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TNO identifier
235044
ISSN
0022-1767
Source
Journal of Immunology, 162 (11), 6912-6918
Document type
article