汉滩病毒（HTNV）感染引起的肾综合征出血热（HFRS）是全球广泛分布且危害极大的一种急性传染病。已知HLA-E限制性CD8+T细胞应答在多种病毒感染中发挥着免疫保护和调节作用，并且HLA-E等位基因在人群中普遍存在，是设计更为特异有效多肽疫苗的首选分子，但目前HTNV特异的HLA-E限制性CD8+T细胞应答研究尚是空白。我们前期预测并筛选出一组HLA-E高亲和力HTNV 结构蛋白9肽。本课题拟在此基础上系统鉴定HLA-E限制性HTNV CD8+T细胞表位并解析HLA-E/表位复合物晶体结构，分析HLA-E限制性HTNV CD8+T细胞发挥免疫保护作用的应答规律，明确HLA-E限制性CD8+T细胞系对效应T细胞的调节作用，揭示HFRS发病过程中HLA-E限制性CD8+T细胞应答发挥免疫保护和调节作用的机制和途径，为临床最终战胜HTNV感染及设计HTNV新型疫苗提供重要的理论依据。

Hemorrhagic fever with renal syndrome (HFRS) induced by Hantaan virus (HTNV) is a serious acute infectious disease distributed globally with great harm. As we known, the HLA-E restricted CD8+T cell response play an important role in many virus infectious diseases through the protection and regulation effects. Moreover, the HLA-E allele, which is common in the population, could be considered as the preferred molecule to be used in the design of the more specific and more effective peptide vaccine. However, so far, the effects and mechanisms of HTNV specific HLA-E restricted CD8+T cell response are still unknown. In our previous work, we have predicted and screened for a group of HLA-E high affinity HTNV 9-mer peptides. In this project, HLA-E restricted HTNV CD8+T cell epitopes will be identified systematically and the crystal structure of HLA-E/epitope complex will be resolved; the frequency of the HLA-E restricted HTNV specific CD8+T cell response in the peripheral blood of HFRS patients will be detected, and the correlation between the responses and the disease severity will be analyzed; the regulating effects of HLA-E restricted HTNV CD8+T cell response to the HTNV specific T cell line will be studied, which will reveal the possible mechanisms of immunoprotection and immunoregulation effects of HLA-E restricted HTNV CD8+T cell response during HFRS. The study may provide the important theoretical basis for finally overcome HTNV infection in clinical, and also for the design of the novel peptides vaccine for HTNV.