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

查看全文 作　　者：Chao [1,2]Hu;Meiying [3]Shen;Xiaojian [1,2]Han;Qian [1,2]Chen;Luo [1,2]Li;Siyin [1,2]Chen;Jing [1,2]Zhang;Fengxia [1,2]Gao;Wang [1,2]Wang;Yingming [1,2]Wang;Tingting [1,2]Li;Shenglong [1,2]Li;Jingjing [1,2]Huang;Jianwei [1,2]Wang;Ju [4]Zhu;Dan [4]Chen;Qingchen [4]Wu;Kun [1,2]Tao;Da [3]Pang;Aishun [1,2]Jin

机构地区：[1]Department of Immunology,College of Basic Medicine,Chongqing Medical University,Chongqing 400016,PR China;[2]Chongqing Key Laboratory of Cancer Immunology Translational Medicine,Chongqing Medical University,Chongqing 400016,PR China;[3]Department of Breast Surgery,Harbin Medical University Cancer Hospital,Harbin,Heilongjiang 150081,PR China;[4]Department of Cardiothoracic Surgery,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,PR China

出　　处：《Genes & Diseases》索引2022年第9卷第1期,共14页

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. 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 functions.Here,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 library.Importantly,we discovered 2 N361-369-specific T cell receptors(TCRs)with high functional avidity that were independent of the CD8 co-receptor.These TCRs exhibited complementary cross-reactivity to several presently reported N361-369 mutant variants,as to the wild-type epitope.Further,the natural functions of these TCRs in the cytotoxic immunity against SARS-CoV-2 were determined with dendritic cells(DCs)and the lung organoid model.We 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 vivo.Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2,and illuminated potential ways of viral clearance in COVID-19 patients.These 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 cells.Additionally,this information is highly relevant for the development of the next-generation vaccines with protections against continuously emerged SARS-CoV-2 mutant strains. 关键词：CD8^(+)T cell HLA class I Lung organoid SARS-CoV-2 T cell epitope TCR

相关文献

参考文献（60）
引证文献（1）
耦合文献（81）

参考文献(60)

引证文献(1)

耦合文献(81)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

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

参考文献(60)

引证文献(1)

耦合文献(81)

用户提示