Dendritic cells infected with Mycobacterium bovis bacillus Calmette Guerinactivate CD8(+) T cells with specificity for a novel mycobacterial epitope

Although CD4(+) T cells are essential for protective immunity against Mycob acterium tuberculosis infection, recent reports indicate that CD8(+) T cell s may also play a critical role in the control of this infection. However, the epitope specificity and the mechanisms of activation of mycobacteria-re active CD8+ T cells are poorly characterized. In order to study the CD8+ T cell responses to the model mycobacterial antigen, MPT64, we used recombina nt vaccinia virus expressing MPT64 (VVWR-64) and a panel of MPT64-derived p eptides to establish that the peptide MPT64(190-198) contains an H-2D(b)-re stricted CD8(+) T cell epitope, A cytotoxic T lymphocyte response to this p eptide could be demonstrated in M, bovis bacillus Calmette Guerin (BCG)-inf ected mice following repeated in vitro stimulation, When bone marrow-derive d dendritic cells (DC) were infected with BCG, the expression of MHC class I molecules by DC was up-regulated in parallel with MHC class Il and B7-2, whereas CD1d expression level was not modified. Moreover, BCG-infected DC a ctivated MPT64(190-198)-specific CD8(+) T cells to secrete IFN-gamma, altho ugh With a lower efficacy than VVWR-64-infected DC. The production of IFN-g amma by MPT64(190-198)-specific CD8(+) T cells was inhibited by antibodies to MHC class I, but not to CD1d, These data suggest that mycobacteria-speci fic CD8+ T cells are primed during infection. Therefore, anti-mycobacterial vaccine strategies targeting the activation of specific CD8(+) T cells by DC may have improved protective efficacy.