PRODUCTION AND CHARACTERIZATION OF HUMAN PROLIFERATIVE T-CELL CLONES SPECIFIC FOR HUMAN PAPILLOMAVIRUS TYPE-1 E4 PROTEIN

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 HI-A-DQ7 and that it can be recognized by T cells with different T-cell receptor gene rearrangements.