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Many pathogenic bacteria invade and multiply within cells. T lymphocytes are critical for an effective immune response to these intracellular pathogens. Infected cells process and present bacterial antigens to T lymphocytes using mechanisms that are interesting and incompletely understood. An excellent model of cellular immunity and bacterial antigen processing is the murine immune response to Listeria monocytogenes. CD8+ cytotoxic T lymphocytes (CTL) are important effectors of immunity to L. monocytogenes infection and recognize bacterial peptides presented by MHC class l molecules on the surface of infected cells. The peptide specificity of three CTL clones has recently been identified. LLO 91-99 derives from the secreted virulence factor listeriolysin and P6O 217-225 comes from the secreted P6O protein. Both are presented to CTL by the H- 2Kd MHC class l molecule. The third epitope, Fr38, is a secreted bacterial peptide that is presented to CTL by the H-2M3 non-classical MHC class l molecule. Preliminary studies show that these three epitopes appear in L. monocytogenes infected cells at different times and in markedly different quantities, and thus their relative contributions to the protective immune response may differ. The proposed studies will investigate the processing and presentation of the three L. monocytogenes CTL epitopes. The effect of cellular infection on MHC class l antigen processing and presentation will be determined. The possibility that the differences between these CTL epitopes may be of relevance to protective immunity will be explored. These studies will enhance our understanding of the CTL response to intracellular pathogens and may suggest new strategies for protection from intracellular pathogens. Additionally, these studies will increase our understanding of the interactions of pathogenic organisms with their mammalian hosts.
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