T-cell response to human papillomavirus type 58 L1, E6 and E7 peptides in women with cleared infection, cervical intraepithelial neoplasia and invasive cancer

Abstract

Human papillomavirus (HPV) 58 exists in a relatively high prevalence in certain parts of the world including East Asia. This study examined T-cell response to HPV 58 L1, E6 and E7 peptides among women with cleared infection, cervical intraepithelial neoplasia (CIN) grade 2 and 3, and invasive cervical cancer (ICC). Peptides found reactive in the in-vitro peptide binding assay or mouse stimulating study were tested with interferon-gamma enzyme-linked immunospot (IFN-gamma ELISPOT) assay to detect peptide-specific response from the peripheral blood mononuclear cells (PBMC) collected from 91 HPV 58-infected women (32 with cleared infection, 16 CIN2, 15 CIN3, and 28 ICC). Four HLA A11-restricted HPV 58 L1 peptides located at amino acid positions 296-304, 327-335, 101-109 and 469-477 showed positive IFN-gamma ELISPOT results, and were mainly from women with cleared infection. Two HLA A11-restricted E6 peptides (amino acid positions 64-72 and 94-102), and three HLA A11-restricted E7 peptides (amino acid positions 78-86, 74-82, and 88-96) showed positive response. Response to E6 and E7 peptides was mainly observed from subjects with CIN2 or above. One HLA A2-restricted E6 peptide located at the amino acid position 99-107 had elicited positive response in two CIN2 subjects. One HLA A24-restricted L1 peptide located at amino acid position 468-476 also elicited positive response in two CIN2 subjects. In summary, this study has identified a few immunogenic epitopes for HPV 58 E6 and E7 proteins. It is worthwhile to further investigate whether response to these epitopes have a role in clearing an established cervical lesion.