SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8(+) T cell activation in COVID-19 patients.
SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8(+) T cell activation in COVID-19 patients.
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DOI：
10.1126/sciimmunol.abf7550
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发表时间：
2021-04-14
影响因子：
24.8
通讯作者：
Hadrup SR
中科院分区：
文献类型：
--
作者：
Saini SK;Hersby DS;Tamhane T;Povlsen HR;Amaya Hernandez SP;Nielsen M;Gang AO;Hadrup SR
在整个SARS-CoV-2基因组中检测到CD8+ T细胞识别，并与COVID-19疾病严重程度相关。T细胞对于有效清除病毒、消灭病毒感染细胞和长期保护疾病至关重要。为了研究COVID-19中CD8+ T细胞免疫的全谱，我们实验评估了覆盖整个SARS-CoV-2基因组的3141个主要组织相容性（MHC） i类结合肽。利用dna条形码多肽- mhc复合物（pMHC）多聚体结合T细胞表型面板，我们报告了122个免疫原性和免疫显性SARS-CoV-2 T细胞表位的综合列表。在COVID-19患者中观察到大量CD8+ T细胞识别，高达27%的CD8+淋巴细胞与sars - cov -2衍生的表位相互作用。大多数免疫原性区域来源于开放阅读框（ORF） 1和ORF3，其中ORF1包含大多数免疫显性表位。在健康供体中也观察到CD8+ T细胞对sars - cov -2衍生表位的低亲和力识别。这种预先存在的T细胞识别特征与在COVID-19患者中观察到的表位景观部分重叠，并可能推动T细胞对SARS-CoV-2感染的反应进一步扩大。重要的是，sars - cov -2特异性CD8+ T细胞的表型揭示了COVID-19患者中强烈的T细胞活化，而在健康个体中观察到最小的T细胞活化。我们发现，与轻度疾病患者相比，重症患者表现出明显更大的sars - cov -2特异性T细胞群，这些T细胞表现出强大的激活谱。这些结果进一步加深了我们对SARS-CoV-2感染的T细胞免疫的理解，并假设强烈的抗原特异性T细胞反应与不同的疾病结局相关。
CD8+ T cell recognition is detected throughout the SARS-CoV-2 genome and is associated with COVID-19 disease severity. T cells are important for effective viral clearance, elimination of virus-infected cells and long-term disease protection. To examine the full-spectrum of CD8+ T cell immunity in COVID-19, we experimentally evaluated 3141 major histocompatibility (MHC) class I-binding peptides covering the complete SARS-CoV-2 genome. Using DNA-barcoded peptide-MHC complex (pMHC) multimers combined with a T cell phenotype panel, we report a comprehensive list of 122 immunogenic and a subset of immunodominant SARS-CoV-2 T cell epitopes. Substantial CD8+ T cell recognition was observed in COVID-19 patients, with up to 27% of all CD8+ lymphocytes interacting with SARS-CoV-2-derived epitopes. Most immunogenic regions were derived from open reading frame (ORF) 1 and ORF3, with ORF1 containing most of the immunodominant epitopes. CD8+ T cell recognition of lower affinity was also observed in healthy donors toward SARS-CoV-2-derived epitopes. This pre-existing T cell recognition signature was partially overlapping with the epitope landscape observed in COVID-19 patients and may drive the further expansion of T cell responses to SARS-CoV-2 infection. Importantly the phenotype of the SARS-CoV-2-specific CD8+ T cells, revealed a strong T cell activation in COVID-19 patients, while minimal T cell activation was seen in healthy individuals. We found that patients with severe disease displayed significantly larger SARS-CoV-2-specific T cell populations compared to patients with mild diseases and these T cells displayed a robust activation profile. These results further our understanding of T cell immunity to SARS-CoV-2 infection and hypothesize that strong antigen-specific T cell responses are associated with different disease outcomes.
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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
MHC I类的性质提出了增强免疫原性的肽。
影响因子：
4.3
作者：
Calis JJ;Maybeno M;Greenbaum JA;Weiskopf D;De Silva AD;Sette A;Keşmir C;Peters B
通讯作者：
Peters B
影响因子：
64.5
作者：
Birnbaum ME;Mendoza JL;Sethi DK;Dong S;Glanville J;Dobbins J;Ozkan E;Davis MM;Wucherpfennig KW;Garcia KC
通讯作者：
Garcia KC
影响因子：
56.9
作者：
Kissler, Stephen M.;Tedijanto, Christine;Lipsitch, Marc
通讯作者：
Lipsitch, Marc
氨基酸相似性说明T细胞交叉反应性和T细胞库中的“孔”。
影响因子：
3.7
作者：
Frankild, Sune;de Boer, Rob J.;Lund, Ole;Nielsen, Morten;Kesmir, Can
通讯作者：
Kesmir, Can