IDENTIFICATION OF A NATURAL T-CELL EPITOPE PRESENTED BY SALMONELLA-INFECTED MACROPHAGES AND RECOGNIZED BY T-CELLS FROM ORALLY IMMUNIZED MICE

Murine infection with Salmonella typhimurium provides models for typho id fever and long-lasting protective immunity conferred by oral vaccin ation with viable attenuated bacteria, To further understand the role of T cells in these systems, we identified a bacterial Ag recognized b y murine T cells responding to a Salmonella infection, From orally inf ected mice, we derived a CD4(+) A(k)-restricted T cell clone (7.4.8) t he stimulatory Ag of which was provided by S. typhimurium or its flage lla, but not by other salmonellae or S. typhimurium mutants unable to synthesize the flagellar filament protein FliC. We mapped antigenic ac tivity to FliC hypervariable region VI using a generally applicable me thod of sequential C-terminal truncation of recombinant MalE-FliC fusi on proteins. Residues 339-350 are the minimal FliC structure capable o f stimulating 7.4.8 and represent the first reported Salmonella-specif ic epitope recognized by T cells from infected mice, T cells with this specificity are generated by oral immunization, reactivity can be rec overed for at least 5 mo afterwards, and FliC is the dominant recall A g for CD4(+) T cells from protectively immunized C3H/HeJ mice, FliC 33 9-350 is presented by macrophages infected with viable S. typhimurium, and presentation, but not bacterial uptake, is greatly enhanced by pr etreatment of macrophages with IFN-gamma, These data point to the impo rtance of IFN-gamma-activated macrophages in the stimulation of T cell s responding to facultative intracellular pathogens like S. typhimuriu m and provide a model system for studying Ag-specific T cell responses in murine salmonellosis.