Identification of HLA-A11-restricted CTL epitopes derived from HPV type 18 using DNA immunization.
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.
Chen
Hsin-Wei
HW
Vaccine Research and Development Center, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Leng
Chih-Hsiang
CH
Liu
Hsin-Yu
HY
Cheng
Wen-Fang
WF
Chang
Yu-Wen
YW
Wu
Pin-Yi
PY
Lien
Shu-Pei
SP
Huang
Tzu-Yi
TY
Chiang
Sheng-Kuo
SK
Lin
Min-Han
MH
Tao
Mi-Hua
MH
Chong
Pele
P
Liu
Shih-Jen
SJ
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
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