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

Published:18 March 2022 DOI: 10.1016/j.isci.2022.103934 PMID: 35194575
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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