Yersinia enterocolitica-mediated translocation of defined fusion proteins to the cytosol of mammalian cells results in peptide-specific MHC class I-restricted antigen presentation

Yersinia enterocolitica delivers a set of effector proteins [Yersinia outer proteins (Yop)] into the cytosol of target cells to modulate host cell sig nal transduction pathways required for the extracellular survival of the ba cterium. Secretion and subsequent translocation of Yop across the eukaryoti c cell membrane are achieved via a type III secretion system. About 50-100 amino acids of the N terminus of Yop ave required for chaperone-directed se cretion and translocation. In this study, it is demonstrated by immunoblot analysis of Yersinia-infected cultured epithelial cells that one ct these p roteins, YopE, can serve as a molecular carrier to deliver protein fragment s of the heterologous p60 antigen of Listeria monocytogenes into the cytoso l of target cells. T cell activation assays revealed that the observed type Ill-mediated antigen translocation led to a p60 peptide-specific MHC class I-restricted antigen presentation. Efficient translocation and antigen pre sentation were strictly dependent on the colocalized expression of hybrid Y opE-p60 proteins and the YopE-specific chaperone SycE. These results sugges t that the Yersinia type III secretion system may serve as an attractive to ol for antigen delivery in Yersinia-based live Vaccines to induce cellular immune responses.