T cell receptor β repertoires in patients with COVID-19 reveal disease severity signatures

Frontiers in Immunology

Immunology

Guo-chao Li¹  Xin-xuan Liu²  Yu Qian²  Fan Liu³  Na Yuan⁴  Ming Chu⁵  Yue-dan Wang⁵  Bo Zhang⁶  Li-ming Cheng⁶  Hong-yan Hou⁶  Hui Hu⁷  Zhong-xin Lu⁷  Qing-gang Ge⁸  Xiao-xiao Li⁸  Chao Li⁸  Chao-ran Dong⁹  Jing Xu^1,10  Yue-jin Yang^1,10  Jin-gang Yang^1,10 

[1] CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China;China National Center for Bioinformation, Beijing, China;CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China;China National Center for Bioinformation, Beijing, China;University of Chinese Academy of Sciences, Beijing, China;CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China;Department of Forensic Sciences, College of Criminal Justice, Naif Arab University of Security Sciences, Riyadh, Saudi Arabia;CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China;University of Chinese Academy of Sciences, Beijing, China;Department of Immunology, School of Basic Medical Sciences, Peking University, NHC Key Laboratory of Medical Immunology (Peking University), Beijing, China;Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department of Pharmacy and Department of Intensive Care Unit, Peking University Third Hospital, Beijing, China;Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital & National Center for Cardiovascular Diseases, Beijing, China;Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China;

关键词: coronavirus disease 2019;    T cells;    T cell receptor β repertoire;    machine learning;    immunology;   

DOI  :  10.3389/fimmu.2023.1190844

 received in 2023-03-21, accepted in 2023-06-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity.MethodsIn this study, we employed high-throughput T cell receptor (TCR) β repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes.ResultsWe observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression.ConclusionsOur study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR β repertoires in monitoring disease development and indicating disease severity.

【 授权许可】

Unknown   
Copyright © 2023 Xu, Li, Yuan, Li, Yang, Cheng, Lu, Hou, Zhang, Hu, Qian, Liu, Li, Wang, Chu, Dong, Liu, Ge and Yang