COMPARTMENTALIZATION OF BACTERIAL-ANTIGENS - DIFFERENTIAL-EFFECTS ON PRIMING OF CD8 T-CELLS AND PROTECTIVE IMMUNITY

Bacterial pathogens synthesize numerous proteins that are either secre ted or localized within bacterial cells. To address the impact of anti gen compartmentalization on T cell immunity, we constructed recombinan t Listeria monocytogenes that express a model CD8 T cell epitope as a secreted or nonsecreted fusion protein. Both forms of the antigen, eit her secreted into the host cell cytoplasm or retained within bacterial cells, efficiently prime CD8 T cell responses. However, epitope-speci fic CD8 T cells confer protection only against bacteria secreting the antigen but not against the bacteria expressing the nonsecreted form o f the same antigen. This dichotomy as a result of antigen compartmenta lization suggests that bacterial antigens are presented by multiple MH C class I pathways to prime CD8 T cells, but only the endogenous pathw ay provides target antigens for CD8 T cell-mediated protective immunit y.