HUMAN T-HELPER CELL EPITOPES OVERLAP B-CELL AND PUTATIVE CYTOTOXIC T-CELL EPITOPES IN THE E2 PROTEIN OF HUMAN PAPILLOMAVIRUS TYPE-16

Activation of T helper cells is a prerequisite for the function of cytotoxic T lymphocytes (CTL) and the maturation of the B cell response. Because epitopes recognized by each of these cells may overlap, we scanned the E2 protein of human papilloma-virus (HPV) type 16 to identify the T helper cell epitopes. Four major T helper cell epitopes (mapping between aa:s 11-25, 141-155, 191-205 and 231-245) and adjacent human B cell epitopes were found. The first peptide-defined epitope (RLNV)(11)CQKILTHYENDSTD(25) over-lapped five putative HLA-I (A1, A2, A0205, A3 and A11) binding motifs (CQDKILTHY, RLNVCQDKI, NVCQDKIL, RLNVCQDK and RLVNCQDK). This epitope is also part of an N-terminal alpha-helix which may form four HLA-II (DR2, DR4, DR7 and DR8) specific agretopes for structures recognizable by the T cell receptor (e.g. KILT). The second epitope (141)EEASVTVVEGOVDYY(155) (GLYY) overlapped the putative HLA-Al and HLA-BW37 binding motifs (VVEGQVDYY/QVDYYGLYY and EEASVTVV), and two HLA-II and (DR1 and DR3) specific agretopes. The third and fourth epitopes were not associated with more than one putative CTL epitope each. Only the first epitope shared considerable aa-homology with corresponding regions of other genital HPV types.