SARS-CoV-2 variant B.1.1.7 caused HLA-A2+ CD8+ T cell epitope mutations for impaired cellular immune response

SARS-CoV-2 变异株 B.1.1.7 导致 HLA-A2+ CD8+ T 细胞表位突变,从而损害细胞免疫反应。

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作者:Chanchan Xiao,Lipeng Mao,Zhigang Wang,Lijuan Gao,Guodong Zhu,Jun Su,Xiongfei Chen,Jun Yuan,Yutian Hu,Zhinan Yin,Jun Xie,Weiqing Ji,Haitao Niu,Feng Gao,Oscar Junhong Luo,Lianbo Xiao,Pengcheng Wang,Guobing Chen

Abstract

Here, we evaluated the immune properties of the HLA-A2 restricted CD8+ T cell epitopes containing mutations from B.1.1.7, and furthermore performed a comprehensive analysis of the SARS-CoV-2 specific CD8+ T cell responses from COVID-19 convalescent patients and SARS-CoV-2 vaccinees recognizing the ancestral Wuhan strain compared to B.1.1.7. First, most of the predicted CD8+ T cell epitopes showed proper binding with HLA-A2, whereas epitopes from B.1.1.7 had lower binding capability than those from the ancestral strain. In addition, these peptides could effectively induce the activation and cytotoxicity of CD8+ T cells. Our results further showed that at least two site mutations in B.1.1.7 resulted in a decrease in CD8+ T cell activation and a possible immune evasion, namely A1708D mutation in ORF1ab1707-1716 and I2230T mutation in ORF1ab2230-2238. Our current analysis provides information that contributes to the understanding of SARS-CoV-2-specific CD8+ T cell responses elicited by infection of mutated strains or vaccination.

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