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Identification of Cross-Reactive CD8+ T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants

Chao Hu, Meiying Shen, View ORCID ProfileXiaojian Han, Qian Chen, Luo Li, Siyin Chen, Jing Zhang, Fengxia Gao, Wang Wang, Yingming Wang, Tingting Li, Shenglong Li, Jingjing Huang, Jianwei Wang, Ju Zhu, Dan Chen, Qingchen Wu, Kun Tao, View ORCID ProfileDa Pang, Aishun Jin
doi: https://doi.org/10.1101/2020.11.02.364729
Chao Hu
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Meiying Shen
3Department of Breast Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Nangang District, Harbin, 150081, China
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Xiaojian Han
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Qian Chen
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Luo Li
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Siyin Chen
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Jing Zhang
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Fengxia Gao
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Wang Wang
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Yingming Wang
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Tingting Li
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Shenglong Li
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Jingjing Huang
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Jianwei Wang
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Ju Zhu
4Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
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Dan Chen
4Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
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Qingchen Wu
4Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
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Kun Tao
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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Da Pang
3Department of Breast Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Nangang District, Harbin, 150081, China
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  • For correspondence: pangda@ems.hrbmu.edu.cn aishunjin@cqmu.edu.cn
Aishun Jin
1Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
2Chongqing Key Laboratory of Cancer Immunology Translational Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China
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  • For correspondence: pangda@ems.hrbmu.edu.cn aishunjin@cqmu.edu.cn
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ABSTRACT

Despite the growing knowledge of T cell responses and their epitopes in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Using a peptide library predicted with HLA class I-restriction, specific CD8+ T cell responses were identified in over 75% of COVID-19 convalescent patients. Among the 15 SARS-CoV-2 epitopes identified from the S and N proteins, N361-369 (KTFPPTEPK) was the most dominant epitope. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity, and they exhibited complementary cross-reactivity to reported N361-369 mutant variants. In dendritic cells (DCs) and the lung organoid model, we found that the N361-369 epitope could be processed and endogenously presented to elicit the activation and cytotoxicity of CD8+ T cells ex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, illuminating natural ways of viral clearance with high relevancy in the vaccine development.

Competing Interest Statement

Patent has been filed for some of the epitopes presented here.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted November 03, 2020.
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Identification of Cross-Reactive CD8+ T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants
Chao Hu, Meiying Shen, Xiaojian Han, Qian Chen, Luo Li, Siyin Chen, Jing Zhang, Fengxia Gao, Wang Wang, Yingming Wang, Tingting Li, Shenglong Li, Jingjing Huang, Jianwei Wang, Ju Zhu, Dan Chen, Qingchen Wu, Kun Tao, Da Pang, Aishun Jin
bioRxiv 2020.11.02.364729; doi: https://doi.org/10.1101/2020.11.02.364729
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Identification of Cross-Reactive CD8+ T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants
Chao Hu, Meiying Shen, Xiaojian Han, Qian Chen, Luo Li, Siyin Chen, Jing Zhang, Fengxia Gao, Wang Wang, Yingming Wang, Tingting Li, Shenglong Li, Jingjing Huang, Jianwei Wang, Ju Zhu, Dan Chen, Qingchen Wu, Kun Tao, Da Pang, Aishun Jin
bioRxiv 2020.11.02.364729; doi: https://doi.org/10.1101/2020.11.02.364729

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