HLA-E-restricted Hantaan virus-specific CD8^(+)T cell responses enhance the control of infection in hemorrhagic fever with renal syndrome  

作　　者：Kang Tang Yusi Zhang Xinyu Li Chunmei Zhang Xiaozhou Jia Haifeng Hu Lihua Chen Ran Zhuang Yun Zhang Boquan Jin Ying Ma 

机构地区：[1]Department of Immunology,The Fourth Military Medical University,Xi’an 710032,China [2]Eighth Hospital of Xi’an,Xi’an 710061,China [3]Department of Infectious Diseases,Tangdu Hospital,The Fourth Military Medical University,Xi’an 710038,China

出　　处：《Biosafety and Health》2023年第5期289-299,共11页生物安全与健康（英文）

基　　金：the National Natural Science Foundation of China,grant number 81871239;Technical Field of Foundation Strengthening Plan Projects,grant number 2019‐JCJQ‐JJ‐094;National Natural Science Foundation of China,grant number 81771705 and 81901600.

摘　　要：Infection with the Hantaan virus(HTNV)may result in severe hemorrhagic fever with renal syndrome(HFRS).The functions of HLA-E-restricted CD8^(+)T lymphocytes in virus control and vaccine development have recently received increased attention.The purpose of this research is to discover HLA-E-restricted CD8^(+)T cell epitopes on HTNV as well as the features of these epitope-specific CD8^(+)T cells in HFRS patients.To anticipate HLA-Erestricted HTNV epitopes,the NetMHCpan servers were utilized.The K562/HLA-E cell binding test and the enzyme-linked immunospot assay were used to confirm epitope binding to HLA-E.The number and features of HLA-E-restricted epitope-specific CD8^(+)T lymphocytes in HFRS patients were investigated using tetramer staining,intracellular cytokine labeling,proliferation,and cytotoxicity assays.Six HTNV-derived HLA-Erestricted CD8^(+)T cell epitopes were found in this study.In mild/moderate HFRS patients,the frequency of HLA-E-restricted epitope-specific CD8^(+)T cells was greater than in severe/critical patients.CD38+HLA-DR+HLA-E-restricted CD8^(+)T cells were identified.Meanwhile,CD45RA^(+)CCR7^(-)effector memory-re-expressing CD45RA T cells with early and intermediate maturation and differentiation characteristics predominated.Notably,CD8^(+)T cells from milder HFRS patients produced more interferon-γ,interleukin-2,and granzyme B,had a stronger proliferative potential,and were inversely linked with the amount of plasma HTNV virus load.Furthermore,HLA-E-restricted epitope-specific CD8^(+)T cells demonstrated improved cytotoxic activity in vitro during the acute stage of HFRS.Taken together,the findings demonstrate the protective effects of HLA-E-restricted CD8^(+)T cells during HTNV infection,suggesting that HLA-E-targeted vaccines against HTNV might be developed for HLA-diverse populations.

关 键 词：Hantaan virus Hemorrhagic fever with renal syndrome HLA‐E CD8+T cells EPITOPE 

分 类 号：R512.8[医药卫生—内科学]