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

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

doi:10.1016/j.isci.2022.103934

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

iScience. 2022 Mar 18;25(3):103934. doi: 10.1016/j.isci.2022.103934. Epub 2022 Feb 17.

Authors

Chanchan Xiao^{1

2}, Lipeng Mao^{1

2}, Zhigang Wang³, Lijuan Gao^{1

2}, Guodong Zhu^{2

4}, Jun Su³, Xiongfei Chen⁵, Jun Yuan⁵, Yutian Hu⁶, Zhinan Yin⁷, Jun Xie^{8

9}, Weiqing Ji^{8

9}, Haitao Niu¹⁰, Feng Gao¹¹, Oscar Junhong Luo^{2

12}, Lianbo Xiao^{8

9}, Pengcheng Wang^{1

2}, Guobing Chen^{1

2

3}

Affiliations

¹ Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510000, China.
² Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, Guangzhou 510000, China.
³ Affiliated Huaqiao Hospital, Jinan University, Guangzhou 510000, China.
⁴ Department of Geriatrics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510000, China.
⁵ Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China.
⁶ Meng Yi Center Limited, Macau 999078, China.
⁷ Biomedical Translational Research Institute, Jinan University, Guangzhou 510000, China.
⁸ ShangHai GuangHua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200052, China.
⁹ Arthritis Institute of Integrated Traditional Chinese and Western Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai University of Chinese Traditional Medicine, Shanghai 200052, China.
¹⁰ School of Medicine & Institute of Laboratory Animal Sciences, Jinan University, Guangzhou 510000, China.
¹¹ School of Medicine, Jinan University, Guangzhou 510000, China.
¹² Department of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou 510000, China.

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 ORF1ab_1707-1716 and I2230T mutation in ORF1ab_2230-2238. 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.

Keywords: Immune response; Virology.