title: Distinct regulation and impact of type 1 T-cell immunity against HPV16 L1, E2 and E6 antigens during HPV16-induced cervical infection and neoplasia.
abstract: Cervical cancer is the possible outcome of a genital infection with high-risk human papillomavirus type 16 (HPV16) and is preceded by a phase of persistent HPV infection during which the host immune system fails to eliminate the virus. Our previous work showed that failure is reflected by the absence of type 1 T-cell immunity against HPV16 early antigens E2 and E6 in patients with HPV16+ cervical lesions. We now show that a majority of both patients with cervical lesions and healthy subjects display HPV16 L1 peptide-specific type 1 T-cell responses with similar magnitude. The T-cell response in patients was directed at a broad range of peptides within L1, suggesting that during persistent or repeated exposure to HPV16 L1, the immune system maximizes its efforts to counter the viral challenge. Unlike the type 1 T-cell responses against HPV16 early antigens E2 and E6, type 1 T-cell immunity against L1 does not correlate with health or disease. This argues that T-cell responses against early and late HPV16 antigens essentially differ in the manner in which they are induced and regulated, as well as in their impact on the subsequent stages of HPV16-induced cervical disease.
authors.affiliation: Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mariëtte I E
authors.initials: MI
authors.lastname: van Poelgeest
authors.forename: Esther R
authors.initials: ER
authors.lastname: Nijhuis
authors.forename: Kitty M C
authors.initials: KM
authors.lastname: Kwappenberg
authors.forename: Ineke E
authors.initials: IE
authors.lastname: Hamming
authors.forename: Jan
authors.initials: J
authors.lastname: Wouter Drijfhout
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: Ate G J
authors.initials: AG
authors.lastname: van der Zee
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Gemma G
authors.initials: GG
authors.lastname: Kenter
authors.forename: Hans W
authors.initials: HW
authors.lastname: Nijman
authors.forename: Rienk
authors.initials: R
authors.lastname: Offringa
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
mesh_terms: D000328:Adult; D000368:Aged; D036022:Capsid Proteins / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology / Q000821:virology; D004268:DNA-Binding Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D012097:Repressor Proteins / 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; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; C063317:L1 protein, Human papillomavirus type 16; D007371:Interferon-gamma