title: Human papillomavirus 16 E7 protein inhibits interferon-γ-mediated enhancement of keratinocyte antigen processing and T-cell lysis.
abstract: Infection of epithelium with human papillomavirus (HPV) 16 is generally prolonged, suggesting an ineffective virus-specific immune response, and prolonged infection promotes anogenital cancer. To determine whether poor antigen presentation by HPV-infected keratinocytes (KCs) contributes to prolonged HPV infection, KCs and KCs expressing HPV 16 E7 protein (E7-KCs) were compared for susceptibility to T-cell-mediated lysis directed to ovalbumin (OVA) processed for presentation by the KCs. Interferon (IFN)-γ efficiently enhanced susceptibility to lysis of KCs presenting OVA, but not of E7-KCs similarly presenting OVA. E7-KCs also exhibited impaired IFN-γ-induced upregulation of transcription of major histocompatibility complex class I antigen processing and presentation-associated genes, and of membrane SIINFEKL-H-2K(b) complexes. Thus, expression of HPV 16 E7 protein in KCs may inhibit enhancement by IFN-γ of KC sensitivity to T-cell lysis, by impairing antigen presentation.
authors.affiliation: The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Qld, Australia.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Graham R
authors.initials: GR
authors.lastname: Leggatt
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D050725:Papillomavirus E7 Proteins / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma