Multiple epitopes from the Mycobacterium tuberculosis ESAT-6 antigen are recognized by antigen-specific human T cell lines

A synthetic-peptide approach was used to map epitope regions of the Mycobac terium tuberculosis 6-kDa early secreted antigen target (ESAT-6) by testing human CD4(+) T cell lines for secretion of IFN-gamma in response to recomb inant ESAT-6 (rESAT-6) and overlapping 20-mer peptides covering the antigen sequence, The results demonstrate that all of the ESAT-6 peptides screened were able to induce IFN-gamma secretion from one or more of the T cell lin es tested. Some of the individual T cell lines showed the capacity to respo nd to all peptides, Human leukocyte antigen (HLA-DR) typing of the donors s howed that rESAT-6 was presented to T cells in association with multiple HL A-DR molecules. The results suggest that frequent recognition of the ill, t uberculosis ESAT-6 antigen by T cells from patients with tuberculosis is du e to the presence of multiple epitopes scattered throughout the ESAT-6 sequ ence.