IDENTIFICATION OF H-2K(B) BINDING AND IMMUNOGENIC PEPTIDES FROM HUMAN PAPILLOMA-VIRUS TUMOR-ANTIGENS E6 AND E7

Peptides can be used to induce MHC class I restricted cytotoxic T cells (CTL) through in vivo immunization. This approach may enable the development of peptide vaccination schemes for immunization against viral infection in humans. Human papillomavirus (HPV) is one of a few viruses associated with human cancer and the development of an anti-cancer vaccine seems possible. As a model approach, we searched the E6 and E7 proteins of the human papillomavirus type 16 for possible murine MHC class I restricted peptide epitopes. We utilized the mouse H2-K-b peptide binding motif which consists of phenylalanine or tyrosine at position five and leucine at the carboxy-terminus with the modification that leucine could be replaced by other aliphatic but non-aromatic amino acids. Four peptide sequences from E6 and two from E7 were selected. These peptides were tested for their ability to bind and stabilize K-b and for their immunogenicity in vivo. It was shown that one peptide from E6, E6.1 (50-57), bound K-b, but was not able to prime mice in vivo. In contrast, the two selected E7 peptides E7.1 (21-28) and E7.2 (48-55) bound K-b and were immunogenic in vivo. The peptide induced CTL lysed syngeneic EL-4 cells transfected with the open reading frame of E7 but not vector only transfectants. This implies that both peptides were naturally processed and presented by K-b on the surface of target cells. MHC class I peptide binding motifs therefore appear to be an effective and useful tool to predict peptide epitopes of proteins associated with cancer.