title: Multiple conformational epitopes are recognized by natural and induced immunity to the E7 protein of human papilloma virus type 16 in man.
abstract: The reactivity of sera from patients with cervical cancer with the E7 protein of human papilloma virus type 16 (HPV16) was estimated using a novel non-radioactive immunoprecipitation assay and four established protein- and peptide-based immunoassays. Six of 14 sera from patients with cervical cancer and 1 of 10 sera from healthy laboratory staff showed repeated reactivity with E7 in at least one assay. Four of the 7 reactive sera were consistently reactive in more than one assay, but only one was reactive in all four assays. Following immunization with E7, 2 of 5 patients with cervical cancer had increased E7-specific reactivity, measurable in one or more assays. No single assay was particularly sensitive for E7 reactivity, or predictive of cervical cancer. Mapping of E7 reactivity to specific E7 peptides was unsuccessful, suggesting that natural or induced E7 reactivity in human serum is commonly directed to conformational epitopes of E7. These results suggest that each assay employed in this study measures a different aspect of E7 reactivity, and that various reactivities to E7 may manifest following HPV infection or immunization. This finding is of significance for monitoring of E7 immunotherapy and for serological screening for cervical cancer.
authors.affiliation: Centre for Immunology and Cancer Research, Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Malcolm
authors.forename: W
authors.initials: W
authors.lastname: Meschede
authors.forename: M
authors.initials: M
authors.lastname: Pawlita
authors.forename: L A
authors.initials: LA
authors.lastname: Koutsky
authors.forename: I H
authors.initials: IH
authors.lastname: Frazer
mesh_terms: D000328:Adult; D000957:Antigens, Viral, Tumor / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D009856:Oncogene Proteins, Viral / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology*; D011487:Protein Conformation; D015531:Radioimmunoprecipitation Assay; D014412:Tumor Virus Infections / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology*
chemical_list: D000957:Antigens, Viral, Tumor; D000939:Epitopes; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16