이창한 (서울대학교 의과대학)

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서울대학교 의과대학

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J. Med. Virol., Nov 2023, 95 (11) | https://doi.org/10.1002/jmv.29199 Tracking antigen-specific TCR clonotypes in SARS-CoV-2 infection reveals distinct severity trajectories

Ik Soo Kim ¹, Chang Kyung Kang ², Seung Jae Lee ³, Chang-Han Lee^4,5,6,7,8, Minji Kim ^4,6,9, Chaehwa Seo ³, Gwanghun Kim ^4,6,9, Soojin Lee^4,6,9, Kyoung Sun Park ⁸, Euijin Chang², Jongtak Jung ^2,10, Kyoung-Ho Song ^2,10, Pyoeng Gyun Choe ², Wan Beom Park ², Eu Suk Kim ^2,10, Hong Bin Kim ^2,10, Nam Joong Kim ², Myoung-Don Oh ², Jong-Eun Lee ³, Hyun Mu Shin ^4,6,8,11, Hang-Rae Kim ^4,6,8,9,11

¹Department of Microbiology, Gachon University College of Medicine, Incheon, South Korea.

²Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.

³DNA Link Inc, Seoul, South Korea.

⁴Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.

⁵Department of Pharmacology, Seoul National University College of Medicine, Seoul, South Korea.

⁶BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, South Korea.

⁷Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

⁸Wide River Institute of Immunology, Seoul National University, Hongcheon, South Korea.

⁹Department of Anatomy & Cell Biology, Seoul National University College of Medicine, Seoul, South Korea.

¹⁰Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.

¹¹Medical Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

Ik Soo Kim, Chang Kyung Kang, Seung Jae Lee, and Chang-Hee Lee contributed equally to this work.

CORRESPONDING AUTHORS : Ik Soo Kim, Hyun Mu Shin, Hang-Rae Kim

Abstract

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.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-03)
연구진국내 연구진
분야 의약학 > 감염의학

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