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.
Darji
A
A
Department of Cell Biology and Immunology, National Center for Biotechnology, Braunschweig, Germany.
Chakraborty
T
T
Wehland
J
J
Weiss
S
S
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001427:Bacterial Toxins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006460:Hemolysin Proteins; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D001427:Bacterial Toxins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D010047:Ovalbumin; C038705:hlyA protein, Listeria monocytogenes