Chemically unrelated mycobacterial peptides as antigens and competitors in antigen recognition by human T cells

Understanding resistance to mycobacterial infectious diseases requires identification of antigens and epitopes (antigenic determinants) that stimulate cell-mediated immune responses. In this study, a DR1-restricted T cell epitope (residues 1 through 20) of the 19-kD protein of M. tuberculosis was identified. Peripheral blood mononuclear cells from two HLA-DR1 patients with tuberculosis responded not only to the 19-kD immunoblot fraction of M. tuberculosis but also to the peptide 1-20. A M. tuberculosis-reactive T cell clone isolated from one of the patient (whose mononuclear cells showed a stronger proliferative response to the 19-kD protein) recognized the peptide 1-20, while failed to recognize a negative control peptide (residues 65 through 85 of the 65-kD mycobacterial protein: peptide 65-85) or a negative control antigen (candida). The antigen recognition to peptide 1-20 was shown to be DR1 restricted. This MHC restriction was confirmed using a DR1-restricted mycobacterial T cell epitope as competitor. These results demonstrated that this mycobacterial competitor significantly reduced the antigen recognition of peptide 1-20. The reduction observed was dose-dependent.