title: HPV-16 E6 and E7 protein T cell epitopes prediction analysis based on distributions of HLA-A loci across populations: an in silico approach.
abstract: Human papillomavirus type 16 (HPV-16) is the most prevalent virus in human cervical cancers, as it is present in more than half of all cases. Many studies have found continued expression of E6 and E7 proteins in the majority of cervical cancer cases, but not in normal tissues. These results indicated that the E6 and E7 proteins could be ideal candidate therapeutic vaccines against HPV-16 infection and cervical cancer. Using the Immune Epitope Database Analysis Resource, cytotoxic T lymphocyte (CTL) epitopes of the HPV-16 E6 and E7 proteins were predicted according to worldwide frequency distributions of HLA-A alleles (HLA-A*01:01, -A*02:01, -A*02:06, -A*03:01, -A*11:01, -A*24:02, -A*26:01, -A*31:01 and -A*33:03). Our results predicted a total of 81 epitopes of HPV-16 E6 (n=59) and E7 (n=22). Epitope cluster analysis showed that among the 20 clusters of HPV-16 E6, cluster 3 contained the most epitopes (10 epitopes), which was represented by HLA-A*31:01 and -A*33:03. Of the 10 clusters of HPV-16 E7, cluster 3 contained the most epitopes (5 epitopes), which was represented by HLA-A*01:01 and -A*26:01. Our results indicated that the combination of epitopes FAFRDLCIVYR₅₂₋₆₂ of E6 (HLA-A*02:06, HLA-A*31:01, and HLA-A*33:03), PYAVCDKCLKF₆₆₋₇₆ of E6 (HLA-A*11:01 and HLA-A*24:02), HGDTPTLHEY₂₋₁₁ of E7 (HLA-A*01:01 and HLA-A*26:01), and YMLDLQPETT₁₁₋₂₀ of E7 (HLA-A*02:01) could vaccinate >50% of all individuals worldwide. Our results propose CTL epitopes or combinations of them predicted in current study for candidate therapeutic vaccines to effectively control HPV-16 infection and development of cervical cancer.
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Yunnan Engineering Research Center of Vaccine Research & Development on Severe Infectious Diseases, Kunming 650118, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yao
authors.forename: Weiwei
authors.initials: W
authors.lastname: Huang
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.forename: Wenjia
authors.initials: W
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Cun
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000595:Amino Acid Sequence; D016000:Cluster Analysis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D015234:HLA-A Antigens / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16