SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8(+) T cells.
SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8(+) T cells.
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SARS-COV-2抗原暴露历史塑造表型和记忆CD8（+）T细胞的特异性。
DOI：
10.1038/s41590-022-01184-4
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发表时间：
2022-05
影响因子：
30.5
通讯作者：
Thomas, Paul G.
中科院分区：
文献类型：
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作者：
Minervina, Anastasia A.;Pogorelyy, Mikhail, V;Kirk, Allison M.;Crawford, Jeremy Chase;Allen, E. Kaitlynn;Chou, Ching-Heng;Mettelman, Robert C.;Allison, Kim J.;Lin, Chun-Yang;Brice, David C.;Zhu, Xun;Vegesana, Kasi;Wu, Gang;Trivedi, Sanchit;Kottapalli, Pratibha;Darnell, Daniel;McNeely, Suzanne;Olsen, Scott R.;Schultz-Cherry, Stacey;Estepp, Jeremie H.;McGargill, Maureen A.;Wolf, Joshua;Thomas, Paul G.
尽管 mRNA 疫苗针对重症 COVID-19 的功效仍然很高，但变种的出现促使人们进行加强免疫。然而，反复接触抗原对 SARS-CoV-2 记忆 T 细胞的影响尚不清楚。在这里，我们利用 MHC 多聚体和 scRNAseq 来分析来自暴露于一种、两种或三种抗原（包括疫苗接种、原发性和突破性感染）的人类的 SARS-CoV-2 反应性 T 细胞。暴露顺序决定了尖峰特异性反应和非尖峰特异性反应之间的分布，感染后接种疫苗会导致尖峰特异性 T 细胞扩增并分化为 CCR7-CD45RA+ 效应细胞。相比之下，突破性感染后的个体会产生强烈的非尖峰特异性反应。对 4,000 多个表位特异性 T 细胞受体序列的分析表明，所有暴露都会引发以共享 TCR 基序为特征的多样化库，并通过单克隆 TCR 表征得到证实，没有证据表明库因重复暴露而缩小。我们的研究结果表明，突破性感染使 T 细胞记忆库多样化，并且当前的疫苗接种方案继续扩大和分化尖峰特异性记忆。
Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence has prompted booster immunizations. However, repeated antigen exposure effects on SARS-CoV-2 memory T cells are poorly understood. Here, we utilize MHC-multimers with scRNAseq to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two, or three antigen exposures, including vaccination, primary, and breakthrough infection. Exposure order determined the distribution between spike- and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7-CD45RA+ effectors. In contrast, individuals after breakthrough infection mount vigorous non-spike-specific responses. Analysis of over 4,000 epitope-specific T cell receptor sequences demonstrates that all exposures elicit diverse repertoires characterized by shared TCR motifs, confirmed by monoclonal TCR characterization, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory.
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影响因子：
16.6
作者：
Kundu R;Narean JS;Wang L;Fenn J;Pillay T;Fernandez ND;Conibear E;Koycheva A;Davies M;Tolosa-Wright M;Hakki S;Varro R;McDermott E;Hammett S;Cutajar J;Thwaites RS;Parker E;Rosadas C;McClure M;Tedder R;Taylor GP;Dunning J;Lalvani A
通讯作者：
Lalvani A
影响因子：
32.4
作者：
Ferretti AP;Kula T;Wang Y;Nguyen DMV;Weinheimer A;Dunlap GS;Xu Q;Nabilsi N;Perullo CR;Cristofaro AW;Whitton HJ;Virbasius A;Olivier KJ Jr;Buckner LR;Alistar AT;Whitman ED;Bertino SA;Chattopadhyay S;MacBeath G
通讯作者：
MacBeath G
影响因子：
82.9
作者：
Ebinger JE;Fert-Bober J;Printsev I;Wu M;Sun N;Prostko JC;Frias EC;Stewart JL;Van Eyk JE;Braun JG;Cheng S;Sobhani K
通讯作者：
Sobhani K
DOI：
10.1038/s41577-022-00676-6
发表时间：
2022-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Flemming A
通讯作者：
Flemming A
影响因子：
24.8
作者：
通讯作者：
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