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高通量测序分析 TCR 文库表明 SARS-CoV-2 感染后 T 细胞免疫反应的特征。

Analysis of TCR Repertoire by High-Throughput Sequencing Indicates the Feature of T Cell Immune Response after SARS-CoV-2 Infection.

机构信息

Department of Immunology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China.

NHC Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.

出版信息

Cells. 2021 Dec 27;11(1):68. doi: 10.3390/cells11010068.


DOI:10.3390/cells11010068
PMID:35011632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8750083/
Abstract

Coronavirus disease 2019 (COVID-19) is a global infectious disease caused by the SARS-CoV-2 coronavirus. T cells play an essential role in the body's fighting against the virus invasion, and the T cell receptor (TCR) is crucial in T cell-mediated virus recognition and clearance. However, little has been known about the features of T cell response in convalescent COVID-19 patients. In this study, using 5'RACE technology and PacBio sequencing, we analyzed the TCR repertoire of COVID-19 patients after recovery for 2 weeks and 6 months compared with the healthy donors. The TCR clustering and CDR3 annotation were exploited to discover groups of patient-specific TCR clonotypes with potential SARS-CoV-2 antigen specificities. We first identified CD4 and CD8 T cell clones with certain clonal expansion after infection, and then observed the preferential recombination usage of V(D) J gene segments in CD4 and CD8 T cells of COVID-19 patients with different convalescent stages. More important, the TRBV6-5-TRBD2-TRBJ2-7 combination with high frequency was shared between CD4 T and CD8 T cells of different COVID-19 patients. Finally, we found the dominant characteristic motifs of the CDR3 sequence between recovered COVID-19 and healthy control. Our study provides novel insights on TCR in COVID-19 with different convalescent phases, contributing to our understanding of the immune response induced by SARS-CoV-2.

摘要

新型冠状病毒肺炎(COVID-19)是由严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引起的全球传染病。T 细胞在机体抵御病毒入侵中发挥着重要作用,而 T 细胞受体(TCR)在 T 细胞介导的病毒识别和清除中至关重要。然而,人们对恢复期 COVID-19 患者 T 细胞反应的特征知之甚少。在这项研究中,我们使用 5'RACE 技术和 PacBio 测序,分析了 COVID-19 患者在康复后 2 周和 6 个月与健康供体相比的 TCR 库。利用 TCR 聚类和 CDR3 注释,发现了具有潜在 SARS-CoV-2 抗原特异性的患者特异性 TCR 克隆型群。我们首先确定了感染后具有特定克隆扩增的 CD4 和 CD8 T 细胞克隆,然后观察了不同恢复期 COVID-19 患者 CD4 和 CD8 T 细胞中 V(D)J 基因片段的优先重组使用。更重要的是,TRBV6-5-TRBD2-TRBJ2-7 组合在不同 COVID-19 患者的 CD4 和 CD8 T 细胞中高频共享。最后,我们发现了恢复期 COVID-19 和健康对照之间 CDR3 序列的优势特征基序。我们的研究为不同恢复期 COVID-19 患者的 TCR 提供了新的见解,有助于我们理解 SARS-CoV-2 诱导的免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f91/8750083/f4a390031618/cells-11-00068-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f91/8750083/6572d15cb99a/cells-11-00068-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f91/8750083/87a31e5ae5a7/cells-11-00068-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f91/8750083/ee52d5d93e18/cells-11-00068-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f91/8750083/f4a390031618/cells-11-00068-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f91/8750083/6572d15cb99a/cells-11-00068-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f91/8750083/87a31e5ae5a7/cells-11-00068-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f91/8750083/ee52d5d93e18/cells-11-00068-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f91/8750083/f4a390031618/cells-11-00068-g004.jpg

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本文引用的文献

[1]
Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients.

Sci Immunol. 2021-8-10

[2]
Comprehensive analysis of TCR repertoire in COVID-19 using single cell sequencing.

Genomics. 2021-3

[3]
SARS-CoV-2 Epitopes Are Recognized by a Public and Diverse Repertoire of Human T Cell Receptors.

Immunity. 2020-11-13

[4]
Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.

Cell. 2020-10-28

[5]
SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition.

Nat Immunol. 2021-1

[6]
Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19.

Cell. 2020-8-14

[7]
Broad and strong memory CD4 and CD8 T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19.

Nat Immunol. 2020-9-4

[8]
SARS-CoV-2-Specific T Cells Exhibit Phenotypic Features of Helper Function, Lack of Terminal Differentiation, and High Proliferation Potential.

Cell Rep Med. 2020-9-22

[9]
Adaptive immune responses to SARS-CoV-2 infection in severe versus mild individuals.

Signal Transduct Target Ther. 2020-8-14

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SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19.

Nature. 2020-7-29

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