HPV18 E1 Protein Plus α-Galactosylceramide Elicit in Mice CD8~+ T Cell Cross-Reactivity Against Cells Expressing E1 from Diverse Human Papillomavirus Types

摘要

CD8~+ T cell immune response plays a critical role in the clearance of human papillomavirus (HPV)-infected cells. During the natural history of HPV infection, the E1 protein, an early-expressed helicase highly conserved among papillomaviruses, is involved in the replication of HPV genomes. We have previously shown, in a murine model, that immunization with HPV 18 E1 protein combined with α-galactosylceramide elicits a specific CD8~+ T cell response. We further proved those findings by analyzing whether CD8~+ T cells from mice immunized with α-galactosylceramide plus HPV18 E1 protein could have a cytotoxic effect on cells expressing the carboxyl-terminal domain from the E1 proteins of other HPV types. Interestingly, CD8~+ T cells raised against HPV 18 E1 antigen presented cross-reactivity against the E1 protein from HPV53, 33, 16, and 31. Poor cross-reactivity was observed for HPV11, and none for HPV6. This outcome may be relevant for the design of broad-spectrum immune-protective agents against HPV infections.