VACCINATION WITH CYTOTOXIC T-LYMPHOCYTE EPITOPE-CONTAINING PEPTIDE PROTECTS AGAINST A TUMOR-INDUCED BY HUMAN PAPILLOMAVIRUS TYPE-16-TRANSFORMED CELLS

Cytotoxic T lymphocyte (CTL) peptide epitopes can be used for immuniza tion of mice against lethal virus infection. To study whether this app roach can be successful against virus-induced tumors we generated a B6 (H-2b) tumorigenic cell line transformed by human papillomavirus (HPV ). This virus is detected in over 90% of all human cervical cancers. T o identify vaccine candidates, we generated a set of 240 overlapping p eptides derived from the HPV type 16 (HPV16) oncogenes E6 and E7. Thes e peptides were tested for their ability to bind H-2K(b) and H-2D(b) M HC class I molecules. Binding peptides were compared with the presentl y known peptide-binding motifs for H-2K(b) and H-2D(b) and the predict ive value of these motifs is shortly discussed. The high-affinity H-2D (b)-binding peptide and putative CTL epitope E7 49-57 (RAHYNIVTF) was used in vaccination studies against HPV 16-transformed tumor cells. Im munization with peptide E7 49-57 rendered mice insensitive to a subseq uent challenge with HPV 16-transformed tumor cells in vivo, and induce d a CTL response which lysed the tumor cells in vitro.