LISTERIOLYSIN GENERATES A ROUTE FOR THE PRESENTATION OF EXOGENOUS ANTIGENS BY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I

We have exploited the pore forming activity of listeriolysin, the hemolysin of Listeria monocytogenes, to activate CD8(+) T cells with soluble proteins in vivo and in vitro. Immunization with soluble, hemolytically active listeriolysin induces both cytotoxic CD8(+) T cells and CD4(+) T cells, and the CD8(+) T cells can be propagated with soluble listeriolysin in vitro. Moreover, conventional antigens like ovalbumin mixed together with listeriolysin are also efficiently introduced into the MHC class I pathway in vitro and in vivo. Hence, listeriolysin effectively directs itself and passenger molecules into the intracellular compartment that leads to the cytotoxic T cell response. In this way, we circumvent the bias of CD8(+) T cells to recognize intracellular antigens presented by major histocompatibility complex class I molecules. As cytotoxic CD8(+) T cells are of pivotal importance in eliminating viral and microbial pathogens, the findings reported here could prove to be useful in vaccine development.