title: Production and characterization of human proliferative T-cell clones specific for human papillomavirus type 1 E4 protein.
abstract: Human papillomavirus type 1 (HPV1) virions and E4 protein purified from cutaneous warts were tested in lymphocyte proliferation assays using normal individuals. Both antigens were found to be capable of eliciting good lymphoproliferative responses. Several T-cell clones specific for wart E4 protein were obtained from a donor who had consistently responded very well to E4 in these initial assays. They were maintained in culture by repeated stimulation with antigen and interleukin-2, using an autologous mitomycin-treated lymphoblastoid cell line as a source of antigen-presenting cells. Two of these clones (3F5 and 4A8), which behaved identically, have been studied in more detail. A series of overlapping synthetic peptides covering the entire E1 E4 protein sequence was used to identify a single T-cell epitope which maps to a strongly hydrophilic region spanning amino acid residues 38 to 50. We have also tested the ability of a panel of major histocompatibility complex class II-matched and -mismatched lymphoblastoid cell lines to present this peptide to the T-cell clones in proliferation assays. The study reports that the epitope is restricted through HLA-DQ7 and that it can be recognized by T cells with different T-cell receptor gene rearrangements.
authors.affiliation: Department of Cancer Studies, Medical School, University of Birmingham, United Kingdom.
authors.forename: J C
authors.initials: JC
authors.lastname: Steele
authors.forename: T
authors.initials: T
authors.lastname: Stankovic
authors.forename: P H
authors.initials: PH
authors.lastname: Gallimore
mesh_terms: D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D002999:Clone Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005802:Genes, MHC Class II / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014860:Warts / Q000382:microbiology
chemical_list: D000939:Epitopes; D006683:HLA-DQ Antigens; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; C056651:oncogene protein E4, human papilloma virus type 1