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
Affiliations
Chanchan Xiao
Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510000, China; Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, Guangzhou 510000, China
Lipeng Mao
Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510000, China; Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, Guangzhou 510000, China
Zhigang Wang
Affiliated Huaqiao Hospital, Jinan University, Guangzhou 510000, China
Lijuan Gao
Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510000, China; Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, Guangzhou 510000, China
Guodong Zhu
Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, Guangzhou 510000, China; Department of Geriatrics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510000, China
Jun Su
Affiliated Huaqiao Hospital, Jinan University, Guangzhou 510000, China
Xiongfei Chen
Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
Jun Yuan
Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
Yutian Hu
Meng Yi Center Limited, Macau 999078, China
Zhinan Yin
Biomedical Translational Research Institute, Jinan University, Guangzhou 510000, China
Jun Xie
ShangHai GuangHua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200052, China; Arthritis Institute of Integrated Traditional Chinese and Western Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai University of Chinese Traditional Medicine, Shanghai 200052, China
Weiqing Ji
ShangHai GuangHua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200052, China; Arthritis Institute of Integrated Traditional Chinese and Western Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai University of Chinese Traditional Medicine, Shanghai 200052, China
Haitao Niu
School of Medicine & Institute of Laboratory Animal Sciences, Jinan University, Guangzhou 510000, China
Feng Gao
School of Medicine, Jinan University, Guangzhou 510000, China
Oscar Junhong Luo
Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, Guangzhou 510000, China; Department of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou 510000, China
Lianbo Xiao
ShangHai GuangHua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200052, China; Arthritis Institute of Integrated Traditional Chinese and Western Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai University of Chinese Traditional Medicine, Shanghai 200052, China; Corresponding author
Pengcheng Wang
Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510000, China; Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, Guangzhou 510000, China; Corresponding author
Guobing Chen
Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510000, China; Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, Guangzhou 510000, China; Affiliated Huaqiao Hospital, Jinan University, Guangzhou 510000, China; Corresponding author
Summary: 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.
