International Immunology, Vol. 13, No. 4, 451-458,
April 2001
© 2001 Japanese Society for Immunology
Dendritic cells infected with Mycobacterium bovis bacillus Calmette Guerin activate CD8+ T cells with specificity for a novel mycobacterial epitope
1 Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag No. 6, Newtown, NSW 2042, Australia
2 Institut Pasteur, Laboratoire d'Ingenierie des Anticorps, 28 Rue du Dr Roux, 75724 Paris Cedex 15, France
3 Department of Medicine, University of Sydney, Sydney, NSW 2006 Australia
Correspondence to: W. J. Britton, Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag No. 6, Newtown, NSW, 2042 Australia
Although CD4+ T cells are essential for protective immunity against Mycobacterium tuberculosis infection, recent reports indicate that CD8+ T cells may also play a critical role in the control of this infection. However, the epitope specificity and the mechanisms of activation of mycobacteria-reactive CD8+ T cells are poorly characterized. In order to study the CD8+ T cell responses to the model mycobacterial antigen, MPT64, we used recombinant vaccinia virus expressing MPT64 (VVWR-64) and a panel of MPT64-derived peptides to establish that the peptide MPT64190–198 contains an H-2Db-restricted CD8+ T cell epitope. A cytotoxic T lymphocyte response to this peptide could be demonstrated in M. bovis bacillus Calmette Guerin (BCG)-infected mice following repeated in vitro stimulation. When bone marrow-derived dendritic cells (DC) were infected with BCG, the expression of MHC class I molecules by DC was up-regulated in parallel with MHC class II and B7-2, whereas CD1d expression level was not modified. Moreover, BCG-infected DC activated MPT64190–198-specific CD8+ T cells to secrete IFN-
, although with a lower efficacy than VVWR-64-infected DC. The production of IFN- by MPT64190–198-specific CD8+ T cells was inhibited by antibodies to MHC class I, but not to CD1d. These data suggest that mycobacteria-specific 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.
Keywords: CD8+ T cells, dendritic cell, epitope, mycobacteria, vaccinia virus
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