CD8 T lymphocytes specific for the secreted p60 antigen protect against Listeria monocytogenes infection

The ability of Listeria monocytogenes to gain access to the cytoplasm of infected cells results in the processing and presentation of bacterial Ags through the MHC class I pathway. As a result, CD8 T cells are the most effective mediators of acquired immunity in the mouse model of L. monocytogenes infection. CD8 T cells specific for a single nonamer epitope derived from the secreted virulence factor listeriolysin O (LLO) can protect H-2d mice against lethal infection. Bacteria lacking LLO are avirulent and do not elicit protective immunity in mice. Thus, the failure of LLO minus L. monocytogenes to elicit protective immunity could be caused either by their inability to enter the cytoplasm or to the lack of LLO-derived peptide epitopes. In this report we provide evidence that H-2d restricted CD8 T cells with specificity for another L. monocytogenes protein, the secreted p60 molecule, can protect against infection. Our studies further demonstrate that LLO-dependent induction of protective immunity results from access of the bacterium to the cytoplasm. In addition, these studies provide support for the hypothesis that secreted bacterial proteins are the most important targets for protective CD8 T cell-mediated immunity.