发热伴血小板减少综合征病毒的人源CD8+ T细胞表位鉴定  

Identification of human CD8+T cell epitope for severe fever with thrombocytopenia syndrome virus

作　　者：李敏 董少波[2] 张杰 岳灿 乔佩雯 喻同琦[2] 梁米芳[1] 占建波[4] 刘军[1] Li Min;Dong Shaobo;Zhang Jie;Yue Can;Qiao Peiwen;Yu Tongqi;Liang Mifang;Zhan Jianbo;Liu Jun(National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China;Office of Health Emergency,Macheng Center for Disease Control and Prevention,Macheng 421181,China;Savaid Medical School,University of Chinese Academy of Sciences,Beijing 100049,China;Institute of Health Inspection and testing,Hubei Center for Disease Control and Prevention,Wuhan 430079,China)

机构地区：[1]中国疾病预防控制中心病毒病预防控制所,北京102206 [2]麻城市疾病预防控制中心应急办,421181 [3]中国科学院大学存济医学院,北京100049 [4]湖北省疾病预防控制中心卫生检验检测研究所,武汉430079

出　　处：《国际病毒学杂志》2021年第2期126-130,共5页International Journal of Virology

基　　金：国家自然科学基金优秀青年基金(81822040);中国医学科学院新发再发病毒适应进化及其防控应用创新单元(2018RU009)。

摘　　要：目的鉴定发热伴血小板减少综合征病毒的CD8^(+)T细胞表位,为了解抗病毒免疫机制和疫苗设计提供参考。方法基于生物信息学方法在SFTSV非结构蛋白中预测潜在表位,利用酶联免疫斑点吸附试验、胞内因子染色、四聚体染色验证表位的免疫原性,体外复性试验验证表位与人白细胞分化抗原的结合力。结果NS-3多肽能刺激特异性CD8^(+)T分泌多种细胞因子,且诱导CD107a表达水平升高。康复病例中检测到NS-3表位特异性CD8^(+)T细胞分群。NS-3与HLA-A*3001能稳定结合。结论从SFTSV的NS蛋白中鉴定到首个人源HLA-A*3001限制性CD8^(+)T细胞表位NS-3,为疫苗开发提供依据。Objective To identify the CD8^(+)T cell epitope of severe fever with thrombocytopenia syndrome virus(SFTSV),so as to understand the mechanism of antiviral immunity and provide reference for vaccine development.Methods Based on bioinformatics method,potential epitopes in nonstructural protein were predicted.The immunogenicity of epitope was verified by enzyme-linked immunospot assay(ELISPOT),intracellular cytokine staining,tetramer staining.The binding ability of epitope to human leukocyte differentiation antigen was verified by in vitro renaturation.Results The NS-3 peptide stimulated specific CD8^(+)T cells to secrete a variety of cytokines,and elevated the expression of CD107a.NS-3 epitope specific CD8^(+)T cell subsets were detected in recovered patient.The NS-3 epitope could bind stably to HLA-A*3001.Conclusions The first human HLA-A*3001 restricted CD8^(+)T cell epitope NS-3 was identified from the NS protein of SFTSV.This provides a basis for vaccine development.

关 键 词：SFTSV 非结构蛋白 CD8+T细胞表位 HLA-A*3001 四聚体 

分 类 号：R558.2[医药卫生—血液循环系统疾病]