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, papilloma virus-like particles (VLPs) gain entry into the cytosol of infected cells and the capsid proteins L1 and L2 can be processed in the MHC class I presentation pathway. Vaccination of mice with human papilloma virus-like particles consisting of capsid proteins L1 and L2 induced a CD8-mediated and perforin dependent protective immune response against a tumor challenge with human papilloma virus transformed tumor cells, which express only minute amounts of L1 protein. Here we show that HPV16 capsid proteins stimulate a MHC 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 least one HLA-A*0201 restricted CTL epitope within the HPV-16 capsid proteins by using a VLP-'infected' HLA-A*0201 transfected human cell line as target cells. These results demonstrated that VLPs can induce a HPV16 capsid protein-specific immune response in humans, allowing the monitoring of immune responses induced by vaccines based on chimeric VLPs carrying additional immunogenic peptides or proteins in therapeutical applications in human patients.
Rudolf
M P
MP
Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University of Chicago, Maywood, IL 60153, USA.
Nieland
J D
JD
DaSilva
D M
DM
Velders
M P
MP
Müller
M
M
Greenstone
H L
HL
Schiller
J T
JT
Kast
W M
WM
D002213:Capsid / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D008297:Male; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014771:Virion
D036022:Capsid Proteins; D015789:HLA-A2 Antigen; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; C063317:L1 protein, Human papillomavirus type 16