title: Low level expression of human papillomavirus type 16 (HPV16) E6 in squamous epithelium does not elicit E6 specific B- or T-helper immunological responses, or influence the outcome of immunisation with E6 protein.
abstract: Mice transgenic for E6/E7 oncogenes of Human Papillomavirus type 16 display life-long expression of E6 in lens and skin epithelium, and develop inflammatory skin disease late in life, which progresses to papillomata and squamous carcinoma in some mice. We asked whether endogenous expression of E6 induced a specific immunological outcome, i.e. immunity or tolerance, or whether the mice remained immunologically naïve to E6. We show that prior to the onset of skin disease, E6 transgenic mice did not develop a spontaneous E6-directed antibody response, nor did they display T-cell proliferative responses to dominant T-helper epitope peptides within E6. In contrast, old mice in which skin disease had arisen, developed antibodies to E6. We also show that following immunisation with E6, specific antibody responses did not differ significantly among groups of E6-transgenic mice of different ages (and therefore of different durations and amounts of exposure to endogenous E6), and non-transgenic controls. Additionally, E6 immunisation-induced T-cell proliferative responses were similar in E6-transgenic and non-transgenic mice. These data are consistent with the interpretation that unimmunised E6-transgenic mice that have not developed inflammatory skin disease remain immunologically naïve to E6 at the B- and Th levels. There are implications for E6-mediated tumorigenesis in humans, and for the development of putative E6 therapeutic vaccines.
authors.affiliation: Centre for Immunology and Cancer Research, University of Queensland, Brisbane, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Azoury-Ziadeh
authors.forename: K
authors.initials: K
authors.lastname: Herd
authors.forename: G J
authors.initials: GJ
authors.lastname: Fernando
authors.forename: P
authors.initials: P
authors.lastname: Lambert
authors.forename: I H
authors.initials: IH
authors.lastname: Frazer
authors.forename: R W
authors.initials: RW
authors.lastname: Tindle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D027383:Papillomaviridae / Q000276:immunology* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D012097:Repressor Proteins; D012867:Skin / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D000914:Antibodies, Viral; C068651:E6 protein, Human papillomavirus type 16; D018984:Epitopes, T-Lymphocyte; D009856:Oncogene Proteins, Viral; D010455:Peptides; D012097:Repressor Proteins