肾综合征出血热(HFRS)是全球广泛分布且危害极大的一种急性传染病。已知细胞免疫应答是机体抗病毒的有效机制之一，但目前对引起HFRS的汉滩病毒(HTNV)特异性T细胞应答研究，仅局限于数个核蛋白特异性CTL表位。我们前期研究工作中预测并合成了我国人群中频率最高的HLA-A2限制性候选HTNV糖蛋白9肽，应用T2细胞结合实验以及酶联免疫斑点实验，系统筛选出一组HLA-A2限制性糖蛋白CTL表位。本课题拟在此基础上，测定HLA-A2限制的HTNV糖蛋白表位特异性CTL在不同病情患者外周血中以及HTNV感染HLA-A2转基因小鼠中的应答水平，分析其与病情的相关性，从而鉴定出能够诱导免疫保护作用的HLA-A2限制性HTNV糖蛋白CTL表位，探讨糖蛋白表位特异性CTL发挥抗病毒作用的途径，阐明HLA-A2限制的糖蛋白特异性CTL保护性免疫应答的规律，为新型HTNV多肽疫苗设计提供重要的理论依据。

Hemorrhagic fever with renal syndrome (HFRS) is a serious acute infectious disease distributed globally with great harm. As we known, the cellular immune response is one of the effective mechanisms in the antivirus process. However, so far, the research on the pathogen Hantaan virus (HTNV) specific T-cell response is limited. Only several HLA restricted CTL epitopes on HTNV nucleocapsid protein have been reported. In our previous work, we used the computer prediction to screen the candidate HTNV glycoprotein (Gn/Gc) 9-mer peptides restricted by HLA-A2, which is the most popular allele in Chinese population. The synthesized candidate peptides were then screened by the T2 cell binding assay and ELISPOT to define a group of HLA-A2 restricted HTNV-Gn/Gc 9-mer epitopes. In this project, the frequency of the HLA-A2 restricted HTNV-Gn/Gc CTL response in the peripheral blood of HFRS patients and in the HLA-A2 transgenic mice infected by the HTNV will be detected, and the correlation between the responses and the disease severity will be analyzed. Thus the HLA-A2 restricted HTNV-Gn/Gc 9-mer epitopes which can cause the immune protective responses in the HFRS will be defined. Then the way and the mechanism through which HTNV-Gn/Gc specific CTL responses can play the antivirus effect will be studied. Base on these results, the research can provide the important theoretical basis for illustration on the principle of the protective immune responses caused by HLA-A2 restricted HTNV-Gn/Gc specific CTL epitopes，and also for the design of the novel peptides vaccine for HTNV.