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Antigenic Cross-Reactivity Between SARS-CoV-2 S1-RBD and Its Receptor ACE2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus responsible for the ongoing COVID-19 pandemic. SARS-CoV-2 binds to the human cell receptor angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain in the S1 subunit of the spike protein (S1-RBD). The...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114768/ https://www.ncbi.nlm.nih.gov/pubmed/35603169 http://dx.doi.org/10.3389/fimmu.2022.868724 |
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author | Lai, Yen-Chung Cheng, Yu-Wei Chao, Chiao-Hsuan Chang, Yu-Ying Chen, Chi-De Tsai, Wei-Jiun Wang, Shuying Lin, Yee-Shin Chang, Chih-Peng Chuang, Woei-Jer Chen, Li-Yin Wang, Ying-Ren Chang, Sui-Yuan Huang, Wenya Wang, Jen-Ren Tseng, Chin-Kai Lin, Chun-Kuang Chuang, Yung-Chun Yeh, Trai-Ming |
author_facet | Lai, Yen-Chung Cheng, Yu-Wei Chao, Chiao-Hsuan Chang, Yu-Ying Chen, Chi-De Tsai, Wei-Jiun Wang, Shuying Lin, Yee-Shin Chang, Chih-Peng Chuang, Woei-Jer Chen, Li-Yin Wang, Ying-Ren Chang, Sui-Yuan Huang, Wenya Wang, Jen-Ren Tseng, Chin-Kai Lin, Chun-Kuang Chuang, Yung-Chun Yeh, Trai-Ming |
author_sort | Lai, Yen-Chung |
collection | PubMed |
description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus responsible for the ongoing COVID-19 pandemic. SARS-CoV-2 binds to the human cell receptor angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain in the S1 subunit of the spike protein (S1-RBD). The serum levels of autoantibodies against ACE2 are significantly higher in patients with COVID-19 than in controls and are associated with disease severity. However, the mechanisms through which these anti-ACE2 antibodies are induced during SARS-CoV-2 infection are unclear. In this study, we confirmed the increase in antibodies against ACE2 in patients with COVID-19 and found a positive correlation between the amounts of antibodies against ACE2 and S1-RBD. Moreover, antibody binding to ACE2 was significantly decreased in the sera of some COVID-19 patients after preadsorption of the sera with S1-RBD, which indicated that antibodies against S1-RBD can cross-react with ACE2. To confirm this possibility, two monoclonal antibodies (mAbs 127 and 150) which could bind to both S1-RBD and ACE2 were isolated from S1-RBD-immunized mice. Measurement of the binding affinities by Biacore showed these two mAbs bind to ACE2 much weaker than binding to S1-RBD. Epitope mapping using synthetic overlapping peptides and hydrogen deuterium exchange mass spectrometry (HDX-MS) revealed that the amino acid residues P463, F464, E465, R466, D467 and E471 of S1-RBD are critical for the recognition by mAbs 127 and 150. In addition, Western blotting analysis showed that these mAbs could recognize ACE2 only in native but not denatured form, indicating the ACE2 epitopes recognized by these mAbs were conformation-dependent. The protein–protein interaction between ACE2 and the higher affinity mAb 127 was analyzed by HDX-MS and visualized by negative-stain transmission electron microscopy imaging combined with antigen-antibody docking. Together, our results suggest that ACE2-cross-reactive anti-S1-RBD antibodies can be induced during SARS-CoV-2 infection due to potential antigenic cross-reactivity between S1-RBD and its receptor ACE2. |
format | Online Article Text |
id | pubmed-9114768 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91147682022-05-19 Antigenic Cross-Reactivity Between SARS-CoV-2 S1-RBD and Its Receptor ACE2 Lai, Yen-Chung Cheng, Yu-Wei Chao, Chiao-Hsuan Chang, Yu-Ying Chen, Chi-De Tsai, Wei-Jiun Wang, Shuying Lin, Yee-Shin Chang, Chih-Peng Chuang, Woei-Jer Chen, Li-Yin Wang, Ying-Ren Chang, Sui-Yuan Huang, Wenya Wang, Jen-Ren Tseng, Chin-Kai Lin, Chun-Kuang Chuang, Yung-Chun Yeh, Trai-Ming Front Immunol Immunology Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus responsible for the ongoing COVID-19 pandemic. SARS-CoV-2 binds to the human cell receptor angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain in the S1 subunit of the spike protein (S1-RBD). The serum levels of autoantibodies against ACE2 are significantly higher in patients with COVID-19 than in controls and are associated with disease severity. However, the mechanisms through which these anti-ACE2 antibodies are induced during SARS-CoV-2 infection are unclear. In this study, we confirmed the increase in antibodies against ACE2 in patients with COVID-19 and found a positive correlation between the amounts of antibodies against ACE2 and S1-RBD. Moreover, antibody binding to ACE2 was significantly decreased in the sera of some COVID-19 patients after preadsorption of the sera with S1-RBD, which indicated that antibodies against S1-RBD can cross-react with ACE2. To confirm this possibility, two monoclonal antibodies (mAbs 127 and 150) which could bind to both S1-RBD and ACE2 were isolated from S1-RBD-immunized mice. Measurement of the binding affinities by Biacore showed these two mAbs bind to ACE2 much weaker than binding to S1-RBD. Epitope mapping using synthetic overlapping peptides and hydrogen deuterium exchange mass spectrometry (HDX-MS) revealed that the amino acid residues P463, F464, E465, R466, D467 and E471 of S1-RBD are critical for the recognition by mAbs 127 and 150. In addition, Western blotting analysis showed that these mAbs could recognize ACE2 only in native but not denatured form, indicating the ACE2 epitopes recognized by these mAbs were conformation-dependent. The protein–protein interaction between ACE2 and the higher affinity mAb 127 was analyzed by HDX-MS and visualized by negative-stain transmission electron microscopy imaging combined with antigen-antibody docking. Together, our results suggest that ACE2-cross-reactive anti-S1-RBD antibodies can be induced during SARS-CoV-2 infection due to potential antigenic cross-reactivity between S1-RBD and its receptor ACE2. Frontiers Media S.A. 2022-05-04 /pmc/articles/PMC9114768/ /pubmed/35603169 http://dx.doi.org/10.3389/fimmu.2022.868724 Text en Copyright © 2022 Lai, Cheng, Chao, Chang, Chen, Tsai, Wang, Lin, Chang, Chuang, Chen, Wang, Chang, Huang, Wang, Tseng, Lin, Chuang and Yeh https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Lai, Yen-Chung Cheng, Yu-Wei Chao, Chiao-Hsuan Chang, Yu-Ying Chen, Chi-De Tsai, Wei-Jiun Wang, Shuying Lin, Yee-Shin Chang, Chih-Peng Chuang, Woei-Jer Chen, Li-Yin Wang, Ying-Ren Chang, Sui-Yuan Huang, Wenya Wang, Jen-Ren Tseng, Chin-Kai Lin, Chun-Kuang Chuang, Yung-Chun Yeh, Trai-Ming Antigenic Cross-Reactivity Between SARS-CoV-2 S1-RBD and Its Receptor ACE2 |
title | Antigenic Cross-Reactivity Between SARS-CoV-2 S1-RBD and Its Receptor ACE2 |
title_full | Antigenic Cross-Reactivity Between SARS-CoV-2 S1-RBD and Its Receptor ACE2 |
title_fullStr | Antigenic Cross-Reactivity Between SARS-CoV-2 S1-RBD and Its Receptor ACE2 |
title_full_unstemmed | Antigenic Cross-Reactivity Between SARS-CoV-2 S1-RBD and Its Receptor ACE2 |
title_short | Antigenic Cross-Reactivity Between SARS-CoV-2 S1-RBD and Its Receptor ACE2 |
title_sort | antigenic cross-reactivity between sars-cov-2 s1-rbd and its receptor ace2 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114768/ https://www.ncbi.nlm.nih.gov/pubmed/35603169 http://dx.doi.org/10.3389/fimmu.2022.868724 |
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