Unbiased Screens Show CD8(+) T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein.
Unbiased Screens Show CD8(+) T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein.
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无偏筛选显示COVID-19患者的CD8(+) T细胞识别SARS-CoV-2中的共享表位，这些表位主要存在于刺突蛋白之外。
DOI：
10.1016/j.immuni.2020.10.006
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发表时间：
2020-11-17
期刊：
影响因子：
32.4
通讯作者：
MacBeath G
中科院分区：
文献类型：
--
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
制定预防或治疗2019冠状病毒病（COVID-19）的有效策略需要了解对严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）的自然免疫反应。我们使用了一种无偏倚的全基因组筛选技术来确定SARS-CoV-2中被COVID-19患者的记忆CD 8 + T细胞识别的精确肽序列。总之，我们为6种最流行的人类白细胞抗原（HLA）类型中的每一种鉴定了3-8个表位。这些表位在患者中广泛共享，并且位于病毒不受突变变异影响的区域。值得注意的是，29个共有表位中只有3个位于刺突蛋白，而大多数表位位于ORF 1ab或核衣壳蛋白。我们还发现，CD 8 + T细胞通常不会与引起普通感冒的四种季节性冠状病毒中的表位发生交叉反应。总的来说，这些发现可以为下一代疫苗的开发提供信息，这些疫苗可以更好地重现对SARS-CoV-2的天然CD 8 + T细胞免疫。无偏见筛选确定了COVID-19患者中CD 8 + T细胞的SARS-CoV-2靶点CD 8 + T细胞主要识别所研究的每种HLA类型的3-8个共享表位。90%的共享表位不位于刺突蛋白中CD 8 + T细胞几乎不与季节性冠状病毒中的表位发生交叉反应Ferretti等人。揭示了COVID-19患者的CD 8 + T细胞广泛共有的特异性SARS-CoV-2表位，但与季节性冠状病毒的交叉反应性有限。大多数表位位于刺突蛋白的外部，这表明可能需要结合这些表位的下一代疫苗来产生更强大和持久的免疫力。
Developing effective strategies to prevent or treat coronavirus disease 2019 (COVID-19) requires understanding the natural immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used an unbiased, genome-wide screening technology to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8+ T cells of COVID-19 patients. In total, we identified 3–8 epitopes for each of the 6 most prevalent human leukocyte antigen (HLA) types. These epitopes were broadly shared across patients and located in regions of the virus that are not subject to mutational variation. Notably, only 3 of the 29 shared epitopes were located in the spike protein, whereas most epitopes were located in ORF1ab or the nucleocapsid protein. We also found that CD8+ T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold. Overall, these findings can inform development of next-generation vaccines that better recapitulate natural CD8+ T cell immunity to SARS-CoV-2. Unbiased screens identified SARS-CoV-2 targets of CD8+ T cells in COVID-19 patients CD8+ T cells predominantly recognize 3–8 shared epitopes for each HLA type studied ∼90% of shared epitopes are not located in the spike protein CD8+ T cells show almost no cross-reactivity with epitopes in seasonal coronaviruses Ferretti et al. reveal specific SARS-CoV-2 epitopes that are broadly shared by CD8+ T cells of COVID-19 patients but exhibit limited cross-reactivity with seasonal coronaviruses. Most epitopes are located outside of the spike protein, suggesting that next-generation vaccines incorporating these epitopes might be needed to generate more robust and durable immunity.
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