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鉴定保守的 SARS-CoV-2 刺突表位，扩大轻症 COVID-19 患者公共 cTfh 克隆型。

Identification of conserved SARS-CoV-2 spike epitopes that expand public cTfh clonotypes in mild COVID-19 patients.

机构信息

Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan.

Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.

出版信息

J Exp Med. 2021 Dec 6;218(12). doi: 10.1084/jem.20211327. Epub 2021 Oct 14.

DOI:10.1084/jem.20211327
PMID:34647971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8641254/
Abstract

Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are a subset of CD4+ T cells that mediate the production of protective antibodies; however, the SARS-CoV-2 epitopes activating Tfh cells are not well characterized. Here, we identified and crystallized TCRs of public circulating Tfh (cTfh) clonotypes that are expanded in patients who have recovered from mild symptoms. These public clonotypes recognized the SARS-CoV-2 spike (S) epitopes conserved across emerging variants. The epitope of the most prevalent cTfh clonotype, S864-882, was presented by multiple HLAs and activated T cells in most healthy donors, suggesting that this S region is a universal T cell epitope useful for booster antigen. SARS-CoV-2-specific public cTfh clonotypes also cross-reacted with specific commensal bacteria. In this study, we identified conserved SARS-CoV-2 S epitopes that activate public cTfh clonotypes associated with mild symptoms.

摘要

适应性免疫是控制 COVID-19 的一个基本组成部分。在这个过程中，滤泡辅助 T（Tfh）细胞是 CD4+T 细胞的一个亚群，介导保护性抗体的产生；然而，激活 Tfh 细胞的 SARS-CoV-2 表位尚未得到很好的描述。在这里，我们鉴定并结晶了从轻度症状恢复的患者中扩增的公共循环滤泡辅助 T（cTfh）克隆型的 TCR。这些公共克隆型识别跨新兴变体保守的 SARS-CoV-2 刺突（S）表位。最常见的 cTfh 克隆型的表位 S864-882 由多种 HLA 呈递并在大多数健康供体中激活 T 细胞，表明该 S 区域是一种通用的 T 细胞表位，可用于增强抗原。SARS-CoV-2 特异性公共 cTfh 克隆型也与特定共生细菌发生交叉反应。在这项研究中，我们鉴定了保守的 SARS-CoV-2 S 表位，这些表位可激活与轻度症状相关的公共 cTfh 克隆型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/c5890c729c04/JEM_20211327_FigS5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/8d9a2de8d05c/JEM_20211327_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/7e3cf81ce5b9/JEM_20211327_FigS3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/aca99c71b102/JEM_20211327_FigS4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/c5890c729c04/JEM_20211327_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/9ecd25d15070/JEM_20211327_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/d58380398f93/JEM_20211327_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/3b39fdd7e331/JEM_20211327_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/6a94395a9b31/JEM_20211327_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/8d9a2de8d05c/JEM_20211327_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/7e3cf81ce5b9/JEM_20211327_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/6713f43c28bf/JEM_20211327_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/aca99c71b102/JEM_20211327_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/a18c20905a37/JEM_20211327_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/8310707b33d4/JEM_20211327_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e7/8641254/c5890c729c04/JEM_20211327_FigS5.jpg

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