HLA-class II-associated control of antigen recognition by T cells in leprosy: a prominent role for the 30/31-kDa antigens.
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.
Thole
J E
JE
Immunohaematology and Bloodbank, Department of Dermatology, Leiden University Medical Center, The Netherlands. j.thole@pg.tno.nl
Janson
A A
AA
Cornelisse
Y
Y
Schreuder
G M
GM
Wieles
B
B
Naafs
B
B
de Vries
R R
RR
Ottenhoff
T H
TH
D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000378:metabolism; D006684:HLA-DR Antigens / Q000502:physiology*; D015803:HLA-DR3 Antigen / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007918:Leprosy / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008970:Molecular Weight; D009166:Mycobacterium leprae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D015803:HLA-DR3 Antigen