Dynamics of TCR repertoire and T cell function in COVID-19 convalescent individuals

Lingjie Luo; Wenhua Liang; Jianfeng Pang; Gang Xu; Yingying Chen; Xinrong Guo; Xin Wang; Yi Zhao; Yangdian Lai; Yang Liu; Bin Li; Bing Su; Shuye Zhang; Michal Baniyash; Lei Shen; Lei Chen; Yun Ling; Ying Wang; Qiming Liang; Hongzhou Lu; Zheng Zhang; Feng Wang

doi:10.1038/s41421-021-00321-x

Dynamics of TCR repertoire and T cell function in COVID-19 convalescent individuals

Cell Discov. 2021 Sep 28;7(1):89. doi: 10.1038/s41421-021-00321-x.

Authors

Lingjie Luo^#^{1

2

3}, Wenhua Liang^#^{1

2

3}, Jianfeng Pang^#^{1

2

3}, Gang Xu^#⁴, Yingying Chen^#¹, Xinrong Guo^{1

2}, Xin Wang^{1

2}, Yi Zhao¹, Yangdian Lai¹, Yang Liu⁴, Bin Li¹, Bing Su^{1

3}, Shuye Zhang⁵, Michal Baniyash⁶, Lei Shen¹, Lei Chen^{1

3}, Yun Ling⁵, Ying Wang¹, Qiming Liang^{1

2}, Hongzhou Lu⁷, Zheng Zhang⁸, Feng Wang^{9

10

11}

Affiliations

¹ Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ The Center for Microbiota and Immunological Diseases, Shanghai Institute of Immunology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China.
⁵ Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
⁶ The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
⁷ Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. luhongzhou@fudan.edu.cn.
⁸ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China. zhangzheng1975@aliyun.com.
⁹ Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wangfeng16@sjtu.edu.cn.
¹⁰ Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wangfeng16@sjtu.edu.cn.
¹¹ The Center for Microbiota and Immunological Diseases, Shanghai Institute of Immunology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wangfeng16@sjtu.edu.cn.

^# Contributed equally.

Abstract

SARS-CoV-2 outbreak has been declared by World Health Organization as a worldwide pandemic. However, there are many unknowns about the antigen-specific T-cell-mediated immune responses to SARS-CoV-2 infection. Here, we present both single-cell TCR-seq and RNA-seq to analyze the dynamics of TCR repertoire and immune metabolic functions of blood T cells collected from recently discharged COVID-19 patients. We found that while the diversity of TCR repertoire was increased in discharged patients, it returned to basal level ~1 week after becoming virus-free. The dynamics of T cell repertoire correlated with a profound shift of gene signatures from antiviral response to metabolism adaptation. We also demonstrated that the top expanded T cell clones (~10% of total T cells) display the key anti-viral features in CD8⁺ T cells, confirming a critical role of antigen-specific T cells in fighting against SARS-CoV-2. Our work provides a basis for further analysis of adaptive immunity in COVID-19 patients, and also has implications in developing a T-cell-based vaccine for SARS-CoV-2.