Clin Vaccine Immunol. 2010 Jul 28. [Epub ahead of print]
Chan PK, Liu SJ, Cheung TH, Yeo W, Ngai SM, Cheung JL, Chong P, Man S.
Departments of Microbiology, Obstetrics and Gynaecology, Clinical Oncology and Biology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Vaccine Development and Research Center, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan; Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, United Kingdom.
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.