title: "Natural" presentation of human papillomavirus type-16 E7 protein to immunocompetent mice results in antigen-specific sensitization or sustained unresponsiveness.
abstract: We have used a mouse model that utilizes the exclusively epithelial nature of human papillomavirus (HPV) infections to investigate the in vivo immune response to the E7 protein of human papillomavirus type-16. A keratinocyte cell line expressing E7 protein has been established and grafted onto syngeneic mice using a transplantation technique that permits the reformation of a differentiated epithelium on a granulation tissue bed. In this way viral antigens may be presented to the immune system in a way comparable to natural infection. A delayed-type hypersensitivity (DTH) response was studied post grafting by intradermal challenge with recombinant E7 protein. A significant response to E7 has been demonstrated in this way; however, priming with a low amount of HPV-16 E7 antigen induces immunological unresponsiveness, as measured by a loss of DTH reactivity to the protein, and persistence of keratinocytes expressing E7. Lymphocytes from mice exhibiting DTH reactivity have been shown to proliferate when stimulated with purified recombinant E7 protein in vitro, while immunoperoxidase staining of tissue from the sites of immunologically-induced inflammation has defined the cell infiltrate to be phenotypically characteristic of DTH. The observations reported here have important implications for vaccine strategy.
authors.affiliation: Department of Pathology, University of Cambridge.
authors.forename: M A
authors.initials: MA
authors.lastname: Chambers
authors.forename: Z
authors.initials: Z
authors.lastname: Wei
authors.forename: N
authors.initials: N
authors.lastname: Coleman
authors.forename: A A
authors.initials: AA
authors.lastname: Nash
authors.forename: M A
authors.initials: MA
authors.lastname: Stanley
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology*; D011994:Recombinant Proteins; D014412:Tumor Virus Infections / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D017931:DNA Primers; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins; C059731:oncogene protein E7, Human papillomavirus type 16