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Tracking antigen-specific TCR clonotypes in SARS-CoV-2 infection reveals distinct severity trajectories

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Kim, Ik Soo; Kang, Chang Kyung; Lee, Seung Jae; Lee, Chang-Han; Kim, Minji; Seo, Chaehwa; Kim, Gwanghun; Lee, Soojin; Park, Kyoung Sun; Chang, Euijin; Jung, Jongtak; Song, Kyoung-Ho; Choe, Pyoeng Gyun; Park, Wan Beom; Kim, Eu Suk; Kim, Hong Bin; Kim, Nam Joong; Oh, Myoung-don; Lee, Jong-Eun; Shin, Hyun Mu; Kim, Hang-Rae

Issue Date
John Wiley & Sons Inc.
Journal of Medical Virology, Vol.95 No.11, p. e29199
Despite the importance of antigen-specific T cells in infectious disease, characterizing and tracking clonally amplified T cells during the progression of a patient's symptoms remain unclear. Here, we performed a longitudinal, in-depth single-cell multiomics analysis of samples from asymptomatic, mild, usual severe, and delayed severe patients of SARS-CoV-2 infection. Our in-depth analysis revealed that hyperactive or improper T-cell responses were more aggressive in delayed severe patients. Interestingly, tracking of antigen-specific T-cell receptor (TCR) clonotypes along the developmental trajectory indicated an attenuation in functional T cells upon severity. In addition, increased glycolysis and interleukin-6 signaling in the cytotoxic T cells were markedly distinct in delayed severe patients compared to usual severe patients, particularly in the middle and late stages of infection. Tracking B-cell receptor clonotypes also revealed distinct transitions and somatic hypermutations within B cells across different levels of disease severity. Our results suggest that single-cell TCR clonotype tracking can distinguish the severity of patients through immunological hallmarks, leading to a better understanding of the severity differences in and improving the management of infectious diseases by analyzing the dynamics of immune responses over time.
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  • College of Medicine
  • Department of Medicine
Research Area Immunology, Infectious Diseases, Vaccination, 감염병, 바이러스질환, 예방접종


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