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Listeriolysin generates a route for the presentation of exogenous antigens by major histocompatibility complex class
A Darji1, T Chakraborty, J Wehland
1Department of Cell Biology and Immunology, National Center for Biotechnology, Braunschweig, Germany.
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.
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.