Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents  

作　　者：Xin Wang Jie Zhang Maoshun Liu Yuanyuan Guo Peipei Guo Xiaonan Yang Bingli Shang Min Li Jinmin Tian Ting Zhang Xi Wang Ronghua Jin Jikun Zhou George F.Gao Jun Liu 

机构地区：[1]Department of Epidemiology,School of Public Health,Cheeloo College of Medicine,Shandong University,Jinan 250012,China [2]NHC Key Laboratory of Biosafety,Research Unit of Adaptive Evolution and Control of Emerging Viruses,Chinese Academy of Medical Sciences,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention(China CDC),Beijing 102206,China [3]Beijing Key Laboratory of Emerging Infectious Diseases,Institute of Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China [4]Beijing Institute of Infectious Diseases,Beijing 100015,China [5]National Center for Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,P.R.China [6]School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou 325035,China [7]School of Ophthalmology&Optometry,Wenzhou Medical University,Wenzhou 325027,China [8]Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry,Guangxi Medical University,Nanning,Guangxi 530021,China [9]Shijiazhuang Fifth Hospital,Shijiazhuang 050011,China [10]CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences(CAS),Beijing 100101,China [11]Savaid Medical School,University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第7期2984-2998,共15页信号转导与靶向治疗（英文）

基　　金：supported by the National Key Research and Development Program of China(2022YFC2604100 to J.L.,and 2023YFC2306003 to X.W.);the National Natural Science Foundation of China(grants 92269203).

摘　　要：The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic.However,the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored.In our research,we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV,identifying cross-reactive CD8^(+)T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays.Then,in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes.Lastly,single-cell T cell receptor reservoir was analyzed based on tetramer staining.Here,we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19,and identified SARS-CoV-2 CD8^(+)T cell epitopes spanning the major structural antigens.T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents.Cross-T cell reactivity was also observed within the identified series of CD8^(+)T cell epitopes.For representative immunodominant peptide pairs,although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar,the TCR repertoires recognizing these peptides were distinct.Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.

关 键 词：IMMUNITY CONSERVED assessed 

分 类 号：R563.1[医药卫生—呼吸系统]