Tracking antigen-specific TCR clonotypes in SARS-CoV-2 infection reveals distinct severity trajectories
© 2023 Wiley Periodicals LLC..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:95 |
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| Enthalten in: |
Journal of medical virology - 95(2023), 11 vom: 02. Nov., Seite e29199 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kim, Ik Soo [VerfasserIn] |
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| Links: |
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| Themen: |
BCR tracking |
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| Anmerkungen: |
Date Completed 03.11.2023 Date Revised 07.11.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/jmv.29199 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM364085347 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 4 | |a TCR tracking | |
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| 650 | 7 | |a Receptors, Antigen, T-Cell |2 NLM | |
| 700 | 1 | |a Kang, Chang Kyung |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Seung Jae |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Chang-Han |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Minji |e verfasserin |4 aut | |
| 700 | 1 | |a Seo, Chaehwa |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Gwanghun |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Soojin |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Kyoung Sun |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Euijin |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, Jongtak |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Kyoung-Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Choe, Pyoeng Gyun |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Wan Beom |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Eu Suk |e verfasserin |4 aut | |
| 700 | 1 | |a Bin Kim, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Nam Joong |e verfasserin |4 aut | |
| 700 | 1 | |a Oh, Myoung-Don |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jong-Eun |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Hyun Mu |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Hang-Rae |e verfasserin |4 aut | |
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