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Background  To identify the novel epitopes from the human papillomavirus type 18 E7 which can sensitize PBMCs of four different major HLA class I A allele.    Methods  Twenty-four synthetic overlapping 15-amino acid peptides were screened by measuring the frequency of CD8 +  cytotoxic T lymphocytes (CTLs)-producing interferon-γ (IFN-γ) by using flow cytometry and ELISpot assays and selected peptides were validated for cytolytic activity by using the  51 Cr release assay. Truncated peptides in the selected epitopes were tested to determine the important residues using ELISpot and  51 Cr release assay.    Results  Among 24 peptides, E7 81-95 DDLRAFQQLFLNTLS (#21) and E7 89-103 LFLNTLSFVCPWCAS (#23) induced significantly higher Th 1 response including IFN-γ production and  in vitro  cytotoxicity of PBMCs of four different HLA-A alleles against cervical cancer cells than that of other peptides and the negative control (no peptide sensitization). In E7 81–95  (#21), amino acid position 81, 82 (N-terminus) and 92, 94, 95 (C-terminus) for HLA-A*02:02 and 24:02, and 81, 82 (N-terminus) and 92, 95 (C-terminus) for HLA-A*11:01 and 33:03 were important to elicit Th1 response of PBMCS. In E7 89–103  (#23), residue 100 and103 (C-terminus) were important to elicit the CD8 +  CTL response in HLA-A*02:01, 11:01 and 33:03 and 100, 101, and 103 (C-terminus) were important to elicit the CD8 +  CTL response in HLA-A*24:02.    Conclusions  E7 81–95  (#21) and E7 89–103  (#23) were identified as novel epitopes from HPV18 E7 which could sensitized PBMCs of four different HLA class I (HLA-A*02:01, 24:02, 11:01 and 33:03). These epitopes could be useful for immune monitoring and immunotherapy for HPV 18+ cervical cancer.

Identification of novel epitopes from human papillomavirus type 18 E7 that can sensitize PBMCs of multiple HLA class I against human cervical cancer