Acquired immunity against intracellular bacteria is T cell dependent. T cells play a major role in protection against intracellular bacteria, but bacterial antigens recognized by T cells have been studied less extensively than bacterial antigens recognized by B cells. Using T lymphocytes from animals immunized against Brucella abortus, we have screened a bacterial genomic library for genes encoding antigens recognized by T cells. Lymphocytes that proliferated to B. abortus proteins were characterized for phenotype and cytokine activity. Bovine and murine lymphocytes recognized common bacterial antigens and possessed similar cytokine profiles, suggesting an analogous immune response in these two animal species. In vivo protection afforded by a particular cell type is dependent on the bacterial antigens presented and mechanisms of antigen presentation. MHC class I and class II gene knockout animals infected with B. abortus have demonstrated that protection to B. abortus is especially dependent on CD8+ T cells. Knowing the cells required for protection, vaccines can be designed to elicit the protective subset of lymphocytes. Currently, we are testing several recombinant B. abortus proteins using different immunization strategies. Finally, bacterial genes activated following intracellular phagocytosis are being examined using a novel, reporter system adapted to B. abortus.