Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19.
Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19.
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DOI：
10.1073/pnas.2201541119
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发表时间：
2022-08-23
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
在对SARS-CoV-2产生病毒特异性免疫反应的同时，残留的B和T细胞多样性是对并发感染和/或癌症产生反应的关键。我们应用了抗原受体测序技术，并提供了一个全面的描述全球免疫库在住院和非住院的个人感染SARS-CoV-2。尽管B细胞多样性可预测地缩小，但仅在50岁以上的人群中意外地观察到αβ和γδ T细胞多样性的显著缩小，这是COVID-19相关死亡率的主要原因。老年人如何对新病毒产生T细胞反应的这种差异可能被认为是老年人的一个风险因素，特别是对于T细胞免疫可能特别重要的新病毒变体。尽管病原体特异性T细胞和B细胞是感染性疾病期间的主要关注焦点，但我们使用COVID-19来询问它们的出现是否以更广泛的B细胞和T细胞库破坏为代价。我们应用基于基因组DNA的方法同时研究了95名个体的免疫球蛋白重链（IGH）和T细胞受体（TCR）β和δ链基因座。我们的方法检测到预期的库集中IGH库，包括扩展的相关序列簇暂时对齐SARS-CoV-2特异性血清转换，并富集一些共享的SARS-CoV-2相关序列。没有明显的年龄相关或疾病严重程度相关的IGH的缺陷。相比之下，尽管聚焦发生在TCRβ和TCRδ位点，包括一些TCRβ序列共享，但破坏性谱系狭窄几乎完全限于许多年龄大于50岁的患者。通过暂时减少T细胞多样性和增加无益T细胞的风险，这些特征可能构成COVID-19的年龄相关风险因素，包括易受新变异的影响，而T细胞可能为新变异提供关键保护。
While making virus-specific immune responses to SARS-CoV-2, residual B and T cell diversity are key to making responses to concurrent co-infections and/or cancers. We applied an antigen receptor–sequencing technology and provide a comprehensive description of the global immune repertoire in hospitalized and nonhospitalized individuals infected with SARS-CoV-2. Although B cell diversity predictably narrowed, significant narrowing of αβ and γδ T cell diversity was unexpectedly observed only in those aged over 50, which is a major inflexion point for COVID-19–associated mortality. Such a discrepancy in how older persons mount T cell responses to a new virus may be considered a risk factor for the elderly, particularly vis-à-vis new virus variants against which T cell immunity may be particularly important. Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) β and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2–specific seroconversion, and enrichment of some shared SARS-CoV-2–associated sequences. No significant age-related or disease severity–related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRβ and TCRδ loci, including some TCRβ sequence–sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.
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影响因子：
8.7
作者：
Corrie BD;Marthandan N;Zimonja B;Jaglale J;Zhou Y;Barr E;Knoetze N;Breden FMW;Christley S;Scott JK;Cowell LG;Breden F
通讯作者：
Breden F
影响因子：
32.4
作者：
Dugan HL;Stamper CT;Li L;Changrob S;Asby NW;Halfmann PJ;Zheng NY;Huang M;Shaw DG;Cobb MS;Erickson SA;Guthmiller JJ;Stovicek O;Wang J;Winkler ES;Madariaga ML;Shanmugarajah K;Jansen MO;Amanat F;Stewart I;Utset HA;Huang J;Nelson CA;Dai YN;Hall PD;Jedrzejczak RP;Joachimiak A;Krammer F;Diamond MS;Fremont DH;Kawaoka Y;Wilson PC
通讯作者：
Wilson PC
影响因子：
3.1
作者：
Christley S;Aguiar A;Blanck G;Breden F;Bukhari SAC;Busse CE;Jaglale J;Harikrishnan SL;Laserson U;Peters B;Rocha A;Schramm CA;Taylor S;Vander Heiden JA;Zimonja B;Watson CT;Corrie B;Cowell LG
通讯作者：
Cowell LG
影响因子：
15.9
作者：
Déchanet, J;Merville, P;Moreau, JF
通讯作者：
Moreau, JF
一种新的高通量测序方法，用于确定T细胞受体（TCR）α和β曲目的多样性和相似性，并确定潜在的新不变TCRα链。
影响因子：
3
作者：
Kitaura K;Shini T;Matsutani T;Suzuki R
通讯作者：
Suzuki R