A new unconventional HLA-A2-restricted epitope from HBV core protein elicits antiviral cytotoxic T lymphocytes  

作　　者：Lu Sun Yu Zhang Bao Zhao Mengmeng Deng Jun Liu Xin Li Junwei Hou Mingming Gui Shuijun Zhang Xiaodong Li George F. Gao Songdong Meng 

机构地区：[1]CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences_ (CAS), Beijing 100101, China [2]Beijing Institute of Infectious Diseases, Beijing 302 Hospital, Beijing 100039, China [3]Xinjiang Agricultural University, Urumqi 830052, China

出　　处：《Protein & Cell》2014年第4期317-327,共11页蛋白质与细胞（英文版）

摘　　要：Cytotoxic T cells （CTLs） play a key role in the control of Hepatitis B virus （HBV） infection and viral clearance. However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia. As HBV core protein （HBc） is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool cov- ering HBc to screen and identify specific CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141- 149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti- HBV activity were further determined in HBV and HLA- A2 transgenic mice. Finally, we show that mutations in HBc141-149 epitope are associated with viral parame- ters and disease progression in HBV infected patients. Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.Cytotoxic T cells （CTLs） play a key role in the control of Hepatitis B virus （HBV） infection and viral clearance. However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia. As HBV core protein （HBc） is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool cov- ering HBc to screen and identify specific CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141- 149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti- HBV activity were further determined in HBV and HLA- A2 transgenic mice. Finally, we show that mutations in HBc141-149 epitope are associated with viral parame- ters and disease progression in HBV infected patients. Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.

关 键 词：chronic hepatitis B HLA-A2 HBc peptideCTL response antiviral cytotoxity 

分 类 号：Q461[生物学—生理学] Q78