Human T-cell responses to HLA-A-restricted high binding affinity peptides of human papillomavirus type 18 proteins E6 and E7

Human Papillomaviruses (HPVs) are sexually transmitted pathogens, which are implicated in the etiology of cervical Cancer. The early proteins E6 and E 7 of HPV have transforming capacity and interfere with the cell cycle contr ol of infected host cells and are essential for the maintenance of the tran sformed state. Identification of MHC class I-restricted, immunogenic peptid es derived from either the E6 or the E7 protein is essential for the design of vaccines as well as the monitoring of clinical trials and immunotherape utic approaches for the treatment of HPV-18-induced carcinomas. We have det ermined the binding affinities for all possible 9-mer peptides spanning the entire E6 and E7 amino acid sequence for the HLA-A*0101, HLA-A*0201, HLA-A *0302, HLA-A*1102, and HLA-A*2402101 molecules by a competition assay with reference peptides, thereby establishing the binding peptides as potential cytotoxic T-cell epitopes, From the HLA-A*0201 binding peptides, we selecte d five E6-derived and one E7-derived peptide with high affinities for HLA-A *0201. These six peptides were tested for their immunogenicity by in vitro immunization assays with purified human CD8+ T cells. We identified three H PV-IS E6-derived peptides (ELTEVFEFA, KTVLELTEV, and KLPDLCTEL) and the E7- derived peptide TLQDIVLHL to be highly immunogenic. Overall, these results will help to design vaccines for the prevention or treatment of HPV-18-indu ced cervical cancer.