Induction of HPV16 capsid protein-specific human T cell responses by virus-like particles

It has been postulated that upon binding to a cell surface receptor, papill oma virus-like particles (VLPs) gain entry into the cytosol of infected cel ls and the capsid proteins L1 and L2 can be processed in the MHC class I pr esentation pathway. Vaccination of mice with human papilloma virus-like par ticles consisting of capsid proteins L1 and L2 induced a CD8-mediated and p erforin dependent protective immune response against a tumor challenge with human papilloma virus transformed tumor cells, which express only minute a mounts of L1 protein. Here we show that HPV16 capsid proteins stimulate a M HC class I restricted CTL response with human peripheral blood lymphocytes (PBL) in vitro. The vigorous response was specific for VLP-infected target cells and was MHC class I restricted. Moreover we show the presence of at l east one HLA-A*0201 restricted CTL epitope within the HPV-16 capsid protein s by using a VLP-'infected' HLA-A*0201 transfected human cell line as targe t cells. These results demonstrated that VLPs can induce a HPV16 capsid pro tein-specific immune response in humans, allowing the monitoring of immune responses induced by vaccines based on chimeric VLPs carrying additional im munogenic peptides or proteins in therapeutical applications in human patie nts.