INDUCTION OF CD8(+) CTL RECOGNIZING MYCOBACTERIAL PEPTIDES

Mycobacterium tuberculosis is the single, most important cause of morb idity attributable to a single infectious organism. CD8(+) T cells pla y an important role in anti-tuberculous immune responses in both mice and humans. Data concerning the identity of mycobacterial antigens rec ognized by CD8(+) T cells is limited; consequently, few CTL epitopes h ave been characterized. The authors identified allele-specific (H-2(b and d)) MHC class I binding motifs in six prominent M. tuberculosis pr otein antigens (the 19 and 38kDa lipoglycoproteins and the 10, 16, 65 and 70 kDa stress proteins). These predicted epitopes were tested for MHC binding as well as their ability to elicit peptide-specific CTL fo llowing in vivo priming. The authors were able to identify eight previ ously undescribed mycobacterial CTL epitopes by using spleen cells fro m peptide-immunized mice. In addition, CTL specific for at least one o f these epitopes also recognized the naturally processed epitope prese nted on transfected EL4 target cells. These mycobacteria-derived CTL e pitopes could be important for future analysis of the involvement of C D8(+) T cells in M. tuberculosis infection, pathogenesis and vaccine d evelopment.