ANTIGEN EXPRESSED BY SALMONELLA-TYPHIMURIUM IS PROCESSED FOR CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX PRESENTATION BY MACROPHAGES BUT NOT INFECTED EPITHELIAL-CELLS

Macrophages were shown to mediate class I major histocompatibility complex (MHC-I) presentation of a fusion protein (Crl-OVA) expressed in Salmonella typhimurium, a bacterium which fails to escape from vacuolar compartments after phagocytosis or penetration into host cells. Salmonella typhimurium also penetrates into non-phagocytic intestinal epithelial cells, a portal of entry for systemic infection. We tested the ability of infected epithelial cells to process antigen expressed by S. typhimurium for presentation by MHC-I molecules to CD8(+) T cells. CMT-93 murine adenocarcinoma cells expressed K-b and effectively presented the OVA 257-264 peptide to CD8 OVA T-hybridoma cells, but infected CMT-93 cells failed to process Crl-OVA expressed in S. typhimurium. Therapeutically useful MHC-I-restricted cytotoxic T-lymphocyte (CTL) responses may be generated by macrophage presentation of Salmonella antigens or recombinant antigens expressed in Salmonella vaccine vectors. Our data suggest that an inability of epithelial cells to present these antigens may limit the utility of CTL in epithelial immunity in salmonellosis, but studies of additional epithelial cell systems are needed.