Antigen presentation of mycobacterial peptides to human T cell clones can be immunomodulated by adding an MHC-specific inhibitor.
The immunomodulation of T cell recognition by mycobacterial antigens was investigated using T cell clones activated with peptide-pulsed EBV-B cells. An HLA-DR1-restricted T cell clone from a patient with tuberculosis responded to peptide 65-85 from the 65-kDa protein of Mycobacterium tuberculosis in a dose-dependent manner, while no significant response was induced by antigen-nonpulsed EBV-B cells or EBV-B cells pulsed with an unrelated antigen (streptokinase/streptodornase). The observed binding to HLA-DR1 could be inhibited when the EBV-B cells were cultured in the presence of an excess of an HLA-DR1-restricted T cell epitope (residues 1-20) from the 19-kDa protein of M. tuberculosis. This inhibition was dose-dependent. In other experiments, proliferation of a DR1-restricted T cell clone from a healthy individual which responded to peptide 1-20 was inhibited by an excess of peptide 65-85, confirming that these peptides are able to compete for the same DR1-binding site. Nevertheless, the T cell clone from the healthy individual showed a relatively lower percentage of inhibition compared with the T cell clone from a patient with tuberculosis. Furthermore, the intensity of this inhibition was reversed as the concentration of stimulatory peptide was increased. The experiments described in this paper demonstrate the immunomodulation of mycobacterial antigen presentation by peptide competition at the level of MHC-binding sites. These data may be important for an understanding of the interactions involved in the mycobacterial cell-mediated immune recognition.
Méndez-Samperio
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Departmento de Inmunologia, Escuela Nacional de Ciencias Biologicas, I.P.N., México, D.F.
D000938:Antigen-Presenting Cells / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D002999:Clone Cells / Q000276:immunology; D015798:HLA-DR1 Antigen / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology
D000942:Antigens, Bacterial; D015798:HLA-DR1 Antigen; D010446:Peptide Fragments