人体感染HCV后约10-30%的个体自发清除病毒，其余转为慢性化，目前影响HCV自然转归的机制尚不清楚。前期发现HLA-DRB1*11:01在汉族和黎族人群中均与HCV自发清除相关，进一步研究显示抗原表位NS3 1088-1103和NS3 1274-1289在自发清除者中引起强烈的CD4+T细胞反应，且抗原表位序列的变异在DRB1*1101+组明显大于DRB1*1101-组，据此推测HLA-DRB1*11:01限制性CD4+T细胞抗原表位在机体清除HCV或慢性化中起重要作用。本项目利用血液中心能获得大量自发清除HCV标本的优势，获得跨越肽段活跃区NS3、NS4和NS5B的DRB1*1101限制性表位，比较其在HCV慢性感染和自发清除者外周血淋巴细胞引起的特异性T细胞免疫反应；探讨限制性表位的变异对特异性T细胞免疫反应的影响，揭示机体自然转归的免疫机制，为HCV疫苗的研制提供肽段储备。

Approximately, 10%-30% of hepatitis C virus (HCV) infected individuals spontaneously clear the virus, while the rests progress to chronic infection. However, the mechanism underlying HCV natural outcome is not fully elucidated. In our previous study, we found that HLA-DRB1*1101 associated with HCV spontaneous clearance both in Han nationality cohort and Li minority cohort. Further studies showed that the antigen epitopes NS3 1088-1103 and NS3 1274-1289 can cause a strong CD4+ T cell response in spontaneous clearer, and the variation of the antigen epitopes sequences in the HLA-DRB1*1101 + group is significantly higher than the DRB1*1101- group. Therefore, we speculate that the HLA-DRB1*1101 restricted CD4+ T cell response plays a critical role in HCV spontaneous clearance and chronic infeciton. Taking the advantage of the massive cases of HCV spontaneous clearance in Guangzhou blood center, this study aims to screen out HLA-DRB1*1101 restricted epitope polypeptides which cover peptide active region(NS3, NS4 and NS5B), compare the extent of T cell immune response stimulated by HLA-DRB1*1101 restricted epitopes between HCV cleared and chronically infected donors, as well as to analyze the impact on the host cellular immune response by the mutations within HLA-DRB1*1101 restricted epitopes of chronic HCV infection to understand the mechanism underlying HCV spontaneous clearance or chronic infection and provide peptide reserves for the development of HCV vaccines.