Identification of cross-reactive CD8^(+)T cell receptors with high functional avidity to a SARS-CoV-2 immunodominant epitope and its natural mutant variants

作     者：Chao Hu Meiying Shen Xiaojian Han Qian Chen Luo Li Siyin Chen Jing Zhang Fengxia Gao Wang Wang Yingming Wang Tingting Li Shenglong Li Jingjing Huang Jianwei Wang Ju Zhu Dan Chen Qingchen Wu Kun Tao Da Pang Aishun Jin Chao Hu;Meiying Shen;Xiaojian Han;Qian Chen;Luo Li;Siyin Chen;Jing Zhang;Fengxia Gao;Wang Wang;Yingmng Wang;Tingting Li;Shenglong Li;Jingjing Huang;Jianwei Wang;Ju Zhu;Dan Chen;Qingchen Wu;Kun Tao;Da Pang;Aishun Jin

作者机构：Department of ImmunologyCollege of Basic MedicineChongqing Medical UniversityChongqing 400016PR China Chongqing Key Laboratory of Cancer Immunology Translational MedicineChongqing Medical UniversityChongqing 400016PR China Department of Breast SurgeryHarbin Medical University Cancer HospitalHarbinHeilongjiang 150081PR China Department of Cardiothoracic SurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016PR China 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2022年第9卷第1期

页      面：216-229页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：This study was supported by the Emergency Project from Chongqing Medical University and Chongqing Medical University fund China(No.X4457)with the donation from Mr Yuling Feng 

主　　题：CD8^(+)T cell HLA class I Lung organoid SARS-CoV-2 T cell epitope TCR 

摘      要：Despite the growing knowledge of T cell responses in COVID-19 patients,there is a lack of detailed characterizations for T cell-antigen interactions and T cell ***,with a predicted peptide library from SARS-CoV-2 S and N proteins,we found that specific CD8+T cell responses were identified in over 75%of COVID-19 convalescent patients(15/20)and an epitope from the N protein,N361-369(KTFPPTEPK),was the most dominant epitope from our selected peptide ***,we discovered 2 N361-369-specific T cell receptors(TCRs)with high functional avidity that were independent of the CD8 *** TCRs exhibited complementary cross-reactivity to several presently reported N361-369 mutant variants,as to the wild-type ***,the natural functions of these TCRs in the cytotoxic immunity against SARS-CoV-2 were determined with dendritic cells(DCs)and the lung organoid *** found that the N361-369 epitope could be normally processed and endogenously presented by these different types of antigen presenting cells,to elicit successful activation and effective cytotoxicity of CD8+T cells ex *** study evidenced potential mechanisms of cellular immunity to SARS-CoV-2,and illuminated potential ways of viral clearance in COVID-19 *** results indicate that utilizing CD8-independent TCRs against SARS-CoV-2-associated antigens may provide functional superiority that is beneficial for the adoptive cell immunotherapies based on natural or genetically engineered T ***,this information is highly relevant for the development of the next-generation vaccines with protections against continuously emerged SARS-CoV-2 mutant strains.