MHC class I restricted T cell responses to Listeria monocytogenes, an intracellular bacterial pathogen

Studies of the murine immune response to infection with the intracellular b acterial pathogen Listeria monocytogenes have provided a wealth of informat ion about innate and acquired immune defenses in the setting of an infectio us disease. Our studies have focused on the MHC class I restricted, CD8(+) T cell responses of Balb/c mice to L. monocytogenes infection. Four peptide s that derive from proteins that L. monocytogenes secretes into the cytosol of infected cells are presented to cytotoxic T lymphocyte (CTL) by the H2- K-d major histocompatibility complex (MHC) class I molecule. We have found that bacterially secreted proteins are rapidly degraded in the host cell cy tosol by proteasomes that utilize, at least in part, the N-end rule to dete rmine the rate of degradation. The MHC class I antigen processing pathway i s remarkably efficient at generating peptides that bind to MHC class I mole cules. The magnitude of in vivo T cell responses, however, is influenced to only a small degree by the amount of antigen or the efficiency of antigen presentation. Measurements of in vivo T cell expansion following L. monocyt ogenes infection indicate that differences in the sizes of peptide-specific T cell responses are more likely owing to differences in the repertoire of naive T cells than to differences in peptide presentation. This notion is supported by our additional finding that dominant T cell populations, expre ss a more diverse T cell receptor (TCR) repertoire than do subdominant T ce ll populations.