Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19.
Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19.
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DOI：
10.3390/diagnostics12051222
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发表时间：
2022-05-13
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
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作者：
测量对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的免疫力，冠状病毒疾病19（COVID-19）的病原体，可以依赖于抗体，反应性T细胞和其他因素，T细胞介导的反应似乎具有更高的灵敏度和寿命。由于每个T细胞携带其T细胞受体（TCR）的基本上独特的核酸序列，我们可以询问来自DNA或RNA的序列数据，以评估免疫应答的各个方面。这篇评论涉及批量，而不是单细胞，TCR库测序的效用，考虑到研究设计的重要性，在队列选择，实验室方法和分析。在理解SARS-CoV-2免疫的进展，导致批量TCR库测序也进行了讨论。通过批量库测序获得的测序数据的复杂性使得分析具有挑战性，但简单的描述性分析、克隆分析、搜索与SARS-CoV-2免疫应答相关的特定序列、基于基序的分析和机器学习方法都已应用。TCR库测序已经证明在活动性感染期间，SARS-CoV-2特异性克隆型的早期扩增随后收缩。TCR库多样性的维持，包括抗SARS-CoV-2应答多样性的维持，预示着有利的结果。严重COVID-19中TCR库缩小最有可能是COVID-19相关淋巴细胞减少症的结果。已经有可能纵向追踪克隆型序列，这对于已知与SARS-CoV-2肽/MHC四聚体结合或与SARS-CoV-2肽诱导的细胞因子应答相关的克隆型特别有价值。与这些先前鉴定的序列密切相关的克隆型已显示在感染期间以类似的动力学响应。通过观察严重COVID-19患者的V节段偏斜以及结构建模，已经确定了SARS-CoV-2刺突蛋白可能的超抗原样作用。这种在其他冠状病毒中明显缺乏的超抗原样活性可能是COVID-19中多系统炎症综合征和细胞因子风暴的基础。批量TCR库测序已被证明是了解SARS-CoV-2与人类宿主之间相互作用的有用且具有成本效益的方法，有可能为治疗和疫苗的设计提供信息，并提供宝贵的致病和流行病学见解。
Measuring immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), can rely on antibodies, reactive T cells and other factors, with T-cell-mediated responses appearing to have greater sensitivity and longevity. Because each T cell carries an essentially unique nucleic acid sequence for its T-cell receptor (TCR), we can interrogate sequence data derived from DNA or RNA to assess aspects of the immune response. This review deals with the utility of bulk, rather than single-cell, sequencing of TCR repertoires, considering the importance of study design, in terms of cohort selection, laboratory methods and analysis. The advances in understanding SARS-CoV-2 immunity that have resulted from bulk TCR repertoire sequencing are also be discussed. The complexity of sequencing data obtained by bulk repertoire sequencing makes analysis challenging, but simple descriptive analyses, clonal analysis, searches for specific sequences associated with immune responses to SARS-CoV-2, motif-based analyses, and machine learning approaches have all been applied. TCR repertoire sequencing has demonstrated early expansion followed by contraction of SARS-CoV-2-specific clonotypes, during active infection. Maintenance of TCR repertoire diversity, including the maintenance of diversity of anti-SARS-CoV-2 response, predicts a favourable outcome. TCR repertoire narrowing in severe COVID-19 is most likely a consequence of COVID-19-associated lymphopenia. It has been possible to follow clonotypic sequences longitudinally, which has been particularly valuable for clonotypes known to be associated with SARS-CoV-2 peptide/MHC tetramer binding or with SARS-CoV-2 peptide-induced cytokine responses. Closely related clonotypes to these previously identified sequences have been shown to respond with similar kinetics during infection. A possible superantigen-like effect of the SARS-CoV-2 spike protein has been identified, by means of observing V-segment skewing in patients with severe COVID-19, together with structural modelling. Such a superantigen-like activity, which is apparently absent from other coronaviruses, may be the basis of multisystem inflammatory syndrome and cytokine storms in COVID-19. Bulk TCR repertoire sequencing has proven to be a useful and cost-effective approach to understanding interactions between SARS-CoV-2 and the human host, with the potential to inform the design of therapeutics and vaccines, as well as to provide invaluable pathogenetic and epidemiological insights.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
DOI：
10.1002/path.5592
发表时间：
2021-03
期刊：
The Journal of pathology
影响因子：
--
作者：
Foers AD;Shoukat MS;Welsh OE;Donovan K;Petry R;Evans SC;FitzPatrick ME;Collins N;Klenerman P;Fowler A;Soilleux EJ
通讯作者：
Soilleux EJ
影响因子：
17.1
作者：
Howie, Bryan;Sherwood, Anna M.;Robins, Harlan S.
通讯作者：
Robins, Harlan S.
影响因子：
8.8
作者：
Dziubianau, M.;Hecht, J.;Babel, N.
通讯作者：
Babel, N.
影响因子：
100.3
作者：
Chen, Zeyu;John Wherry, E.
通讯作者：
John Wherry, E.