Characterization of a Mycobacterium tuberculosis peptide that is recognized by human CD4⁺ and CD8⁺ T cells in the context of multiple HLA alleles

The secreted Mycobacterium tuberculosis 10-kDa culture filtrate protein (CFP)10 is a potent T cell Ag that is recognized by a high percentage of persons infected with M. tuberculosis. We determined the molecular basis for this widespread recognition by identifying and characterizing a 15-mer peptide, CFP10_71-85, that elicited IFN-γ production and CTL activity by both CD4⁺ and CD8⁺ T cells from persons expressing multiple MHC class II and class I molecules, respectively. CFP10_71-85 contained at least two epitopes, one of 10 aa (peptide T1) and another of 9 aa (peptide T6). T1 was recognized by CD4⁺ cells in the context of DRB1*04, DR5*0101, and DQB1*03, and by CD8⁺ cells of A2⁺ donors. T6 elicited responses by CD4⁺ cells in the context of DRB1*04 and DQB1*03, and by CD8⁺ cells of B35⁺ donors. Deleting a single amino acid from the amino or carboxy terminus of either peptide markedly reduced IFN-γ production, suggesting that they are minimal epitopes for both CD4⁺ and CD8⁺ cells. As far as we are aware, these are the shortest microbial peptides that have been found to elicit responses by both T cell subpopulations. The capacity of CFP10_71-85 to stimulate IFN-γ production and CTL activity by CD4⁺ and CD8⁺ cells from persons expressing a spectrum of MHC molecules suggests that this peptide is an excellent candidate for inclusion in a subunit antituberculosis vaccine.