Distinct regulation and impact of type 1 T-cell immunity against HPV16 L1, E2 and E6 antigens during HPV16-induced cervical infection and neoplasia.
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.
van Poelgeest
Mariëtte I E
MI
Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
Nijhuis
Esther R
ER
Kwappenberg
Kitty M C
KM
Hamming
Ineke E
IE
Wouter Drijfhout
Jan
J
Fleuren
Gert Jan
GJ
van der Zee
Ate G J
AG
Melief
Cornelis J M
CJ
Kenter
Gemma G
GG
Nijman
Hans W
HW
Offringa
Rienk
R
van der Burg
Sjoerd H
SH
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
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