Definition of a human suppressor T-cell epitope.

Abstract

The The clinical spectrum of leprosy reflects the striking differences between individuals in developing cell-mediated immunity to the causative agent, Mycobacterium leprae (7,8). At the "high resistant" pole of this spectrum, tuberculoid leprosy (TT) patients develop strong cellular immune responses to M. leprae antigens and efficiently eliminate the bacilli, whereas at the "low resistant" pole, lepromatous leprosy (LL) patients fail to mount specific T-cell responses to M. leprae antigens and develop a multibacillary disseminated disease (9). Several lines of evidence suggest that the M. leprae-specific T-cell nonresponsiveness observed in LL patients is not due to an absence ofM. leprae-reactive T cells or to defective antigen presentation as claimed in earlier reports (10, 11) but may be due to active down-regulation of M. leprae-specific T-cell responses, presumably by suppressor T (Ts) cells induced by M. leprae (12-14). Supporting this latter premise, we and others have previously isolated CD4+ and CD8+ T-cell clones from the peripheral blood and skin lesions of LL patients and shown that these T cells specifically suppress mycobacterium-specific T-cell responses in vitro (15-17). Previous analyses of these Ts clones revealed that they, like M. leprae-induced Th cells, express T-cell receptor (TCR) a and , ( chains and are restricted by HLA-DR or HLA-DQ molecules (15,16,18,38

HLA-DRB1 leprogenic motifs in Nigerian population groups

“…Response to M. leprae infection can therefore be said to rely largely on the HLA-DR motif presenting the peptide to T cells with specific CDR3 motifs on the T cell. Data from other workers [29,31] also support this conclusion.…”

Identification of a human CD8+regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4

“…Furthermore, suppressor CD8 ϩ T cell clones from immunologically unresponsive individuals with leprosy suppressed Th1 responses (14,24).…”

“…Bacillus Calmette-Guérin's inadequacy as TB vaccine may, similarly, at least in part (10), be accounted for by its ability to induce Tregs (11). Tregs have been isolated from leprosy patients (12,13), which suppressed CD4 ϩ Th1 cells (12)(13)(14). More recently, IL-10-producing T cells were reported in anergic TB patients (15), and increased frequencies of CD4 ϩ CD25 HI T cells have been found in the circulation of TB patients (16,17).…”

Genetics of susceptibility to leprosy

“…47 Alternatively, peptide presentation by specific class II molecules may result in activation of suppressor/regulatory T-cells. 49 Transporter 2, ATP-binding cassette, sub-family B (TAP2). TAP2 is critical for peptide translocation from the cytosol into the endoplasmic reticulum and for peptide binding to MHC class I molecules.…”