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CD8+ T cell epitope variations suggest a potential antigen presentation deficiency for spike protein of SARS-CoV-2
bioRxiv - Immunology Pub Date : 2021-01-24 , DOI: 10.1101/2021.01.22.427863
Congling Qiu , Chanchan Xiao , Zhigang Wang , Xiongfei Chen , Lijuan Gao , Jieping Deng , Jun Su , Huanxing Su , Evandro Fei Fang , Zhang-Jin Zhang , Guodong Zhu , Jikai Zhang , Caojun Xie , Jun Yuan , Oscar Junhong Luo , Pengcheng Wang , Guobing Chen

COVID-19 is caused by a newly identified coronavirus, SARS-CoV-2, and has become a pandemic around the world. The illustration of the immune responses against SARS-CoV-2 is urgently needed for understanding the pathogenesis of the disease and its vaccine development. CD8+ T cells are critical for virus clearance and induce long lasting protection in the host. Here we identified specific HLA-A2 restricted T cell epitopes in the spike protein of SARS-CoV-2. Seven epitope peptides (n-Sp1, 2, 6, 7, 11, 13, 14) were confirmed to bind with HLA-A2 and potentially be presented by antigen presenting cells to induce host immune responses. Tetramers containing these peptides could interact with specific CD8+ T cells from convalescent COVID-19 patients, and one dominant epitope (n-Sp1) was defined. In addition, these epitopes could activate and generate epitope-specific T cells in vitro, and those activated T cells showed cytotoxicity to target cells. Meanwhile, all these epitopes exhibited high frequency of variations. Among them, n-Sp1 epitope variation 5L>F significantly decreased the proportion of specific T cell activation; n-Sp1 epitope 8L>V variant showed significantly reduced binding to HLA-A2 and decreased the proportion of n-Sp1-specific CD8+ T cell, which potentially contributes to the immune escape of SAR-CoV-2.

中文翻译:

CD8 + T细胞表位变异表明SARS-CoV-2突触蛋白可能存在抗原呈递不足

COVID-19是由新发现的冠状病毒SARS-CoV-2引起的,并已在世界范围内流行。迫切需要对SARS-CoV-2的免疫应答进行说明,以了解该疾病的发病机理及其疫苗开发。CD8 + T细胞对于清除病毒至关重要,并在宿主中诱导长期持续的保护。在这里,我们在SARS-CoV-2的突触蛋白中鉴定了特定的HLA-A2限制性T细胞表位。证实七个表位肽(n-Sp1、2、6、7、11、13、14)与HLA-A2结合,并可能由抗原呈递细胞呈递以诱导宿主免疫应答。含有这些肽的四聚体可以与来自恢复期COVID-19患者的特定CD8 + T细胞相互作用,并定义了一个显性表位(n-Sp1)。此外,这些表位可以在体外活化并产生表位特异性T细胞,而这些活化的T细胞对靶细胞显示出细胞毒性。同时,所有这些表位均表现出高频率的变异。其中,n-Sp1表位变异5L> F显着降低了特异性T细胞活化的比例;n-Sp1表位8L> V变异体显示出与HLA-A2的结合显着降低,n-Sp1特异性CD8 + T细胞的比例降低,这可能有助于SAR-CoV-2的免疫逃逸。
更新日期:2021-01-25
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