title: Identification of HLA-A11-restricted CTL epitopes derived from HPV type 18 using DNA immunization.
abstract: Identification of the cytotoxic T lymphocyte (CTL) epitopes of tumor antigens is important for effective immunotherapy. We report that a combination of epitope prediction, enzyme-linked immunosorbent assay (ELISA)-based epitope-HLA complex formation, and DNA immunization methods can improve the efficiency and accuracy of CTL epitope studies. In this study, two HLA-A11-restricted epitopes derived from human papillomavirus (HPV)18 E6 oncoprotein were identified. HLA-A11-transgenic mice immunized with these epitopes could specifically induce interferon-gamma (IFNgamma) production, cytotoxicity and peptide/HLA-A11 tetramer binding in CD8(+) T-cells. To study intracellular processing of CTL epitopes, we constructed a DNA plasmid containing an endoplasmic reticulum (ER) targeting sequence as well as the HPV18 E6 and E7 genes (pEK/HPV18E6E7). CTL responses against peptide-pulsed T2/A11 cells could be detected after immunizing HLA-A11-transgenic mice with pEK/HPV18E6E7. Furthermore, the identified peptides could stimulate T-cells to secrete IFNgamma from HPV18-infected patients. Our results demonstrate that the antigenic E6 peptides derived from HPV18 are potential candidates for the treatment of HPV 18-associated tumors in HLA-A11(+) populations.
authors.affiliation: Vaccine Research and Development Center, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Chen
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Leng
authors.forename: Hsin-Yu
authors.initials: HY
authors.lastname: Liu
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chang
authors.forename: Pin-Yi
authors.initials: PY
authors.lastname: Wu
authors.forename: Shu-Pei
authors.initials: SP
authors.lastname: Lien
authors.forename: Tzu-Yi
authors.initials: TY
authors.lastname: Huang
authors.forename: Sheng-Kuo
authors.initials: SK
authors.lastname: Chiang
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Lin
authors.forename: Mi-Hua
authors.initials: MH
authors.lastname: Tao
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology*; D059870:HLA-A11 Antigen; D052161:Human papillomavirus 18 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D009842:Oligopeptides; D009856:Oncogene Proteins, Viral; D019444:Vaccines, DNA