title: E7 oncoprotein of human papillomavirus type 16 expressed constitutively in the epidermis has no effect on E7-specific B- or Th-repertoires or on the immune response induced or sustained after immunization with E7 protein.
abstract: A line of FVB (H-2q) mice transgenic for the E6/E7 open reading frames of Human Papillomavirus type 16 driven from the alpha-A crystallin promoter expresses E7 mRNA in lens and skin epithelium. E7 protein is detectable in adult skin, coinciding with the development of inflammatory skin disease, which progresses to papillomata and squamous carcinomata in some mice. By examining the outcome of parenteral immunization with E7 protein, we sought to determine whether endogenous expression of E7 in skin had induced a preexisting immune outcome, i.e., specific immunity or tolerance, or whether the mice remain naive ("ignorant") to E7. Our data show that the antibody response to defined E7 B-epitopes, the proliferative response to Th epitopes, and the delayed-type hypersensitivity (DTH) response to whole E7 did not differ between groups of young and old E6/E7 transgenic mice (likely having different degrees of lifetime exposure to E7 protein) or between E6/E7-transgenic and nontransgenic parental strain control mice. Although an E7-specific CTL response could not be induced in the H-2q background of these mice, incorporation of a Db allele into the genome allowed comparison of Db-restricted CTL responses in E6/E7 transgenic and nontransgenic mice. Experiments indicated that the E7-immunization-induced CTL response did not differ significantly between E6/E7 transgenic and nontransgenic mice. We interpret these results to indicate that in spite of expression of E7 protein in adult skin, E6/E7 transgenic mice remain immunologically naive (ignorant) of E7 epitopes presented by immunization.
authors.affiliation: Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Herd
authors.forename: G J
authors.initials: GJ
authors.lastname: Fernando
authors.forename: L A
authors.initials: LA
authors.lastname: Dunn
authors.forename: I H
authors.initials: IH
authors.lastname: Frazer
authors.forename: P
authors.initials: P
authors.lastname: Lambert
authors.forename: R W
authors.initials: RW
authors.lastname: Tindle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D004817:Epidermis; D006801:Humans; D006968:Hypersensitivity, Delayed; D007114:Immunization; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control; D012097:Repressor Proteins; D012867:Skin / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology / Q000517:prevention & control
chemical_list: D000914:Antibodies, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16