论文题目: | A new unconventional HLA-A2-restricted epitope from HBV core protein elicits antiviral cytotoxic T lymphocytes |
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作者: | Sun Lu, Zhang Yu, Zhao Bao, Deng Mengmeng, Liu Jun, Li Xin, Hou Junwei, Gui Mingming, Zhang Shuijun, Li Xiaodong, George F Gao*, Meng Songdong* |
联系作者: | George F Gao*, Meng Songdong* |
刊物名称: | Protein Cell |
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年份: | 2014 |
影响因子: | 3.22 |
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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 covering 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 parameters 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. |
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