title: T-cell response to human papillomavirus type 58 L1, E6, And E7 peptides in women with cleared infection, cervical intraepithelial neoplasia, or invasive cancer.
abstract: Human papillomavirus type 58 (HPV-58) exists in a relatively high prevalence in certain parts of the world, including East Asia. This study examined the T-cell response to HPV-58 L1, E6, and E7 peptides among women with cleared infection, cervical intraepithelial neoplasia grade 2 (CIN2) or CIN3, or invasive cervical cancer (ICC). Peptides found to be reactive in the in vitro peptide binding assay or mouse-stimulating study were tested with a gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay to detect peptide-specific responses 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 to 304, 327 to 335, 101 to 109, and 469 to 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 to 72 and 94 to 102) and three HLA-A11-restricted E7 peptides (amino acid positions 78 to 86, 74 to 82, and 88 to 96) showed a positive response. A response to E6 and E7 peptides was mainly observed from subjects with CIN2 or above. One HLA-A2-restricted E6 peptide, located at amino acid position 99 to 107, elicited a positive response in two CIN2 subjects. One HLA-A24-restricted L1 peptide, located at amino acid position 468 to 476, also elicited a 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 responses to these epitopes have a role in clearing an established cervical lesion.
authors.affiliation: Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region, China. paulkschan@cuhk.edu.hk
authors.forename: Paul K S
authors.initials: PK
authors.lastname: Chan
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Liu
authors.forename: T H
authors.initials: TH
authors.lastname: Cheung
authors.forename: Winnie
authors.initials: W
authors.lastname: Yeo
authors.forename: S M
authors.initials: SM
authors.lastname: Ngai
authors.forename: Jo L K
authors.initials: JL
authors.lastname: Cheung
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.forename: Stephen
authors.initials: S
authors.lastname: Man
mesh_terms: D000328:Adult; D001208:Asia; D036022:Capsid Proteins / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000821:virology*
chemical_list: D036022:Capsid Proteins; C548991:E6 protein, human papillomavirus type 58; D018984:Epitopes, T-Lymphocyte; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D007371:Interferon-gamma