Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals
Abstract The COVID-19 pandemic has revealed a range of disease phenotypes in infected patients with asymptomatic, mild, or severe clinical outcomes, but the mechanisms that determine such variable outcomes remain unresolved. In this study, we identified immunodominant CD8 T-cell epitopes in the spik...
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2021
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oai:doaj.org-article:0e59e27035f7492798884ba134ab486f2021-12-02T17:45:03ZImmunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals10.1038/s41598-021-92521-42045-2322https://doaj.org/article/0e59e27035f7492798884ba134ab486f2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92521-4https://doaj.org/toc/2045-2322Abstract The COVID-19 pandemic has revealed a range of disease phenotypes in infected patients with asymptomatic, mild, or severe clinical outcomes, but the mechanisms that determine such variable outcomes remain unresolved. In this study, we identified immunodominant CD8 T-cell epitopes in the spike antigen using a novel TCR-binding algorithm. The predicted epitopes induced robust T-cell activation in unexposed donors demonstrating pre-existing CD4 and CD8 T-cell immunity to SARS-CoV-2 antigen. The T-cell reactivity to the predicted epitopes was higher than the Spike-S1 and S2 peptide pools in the unexposed donors. A key finding of our study is that pre-existing T-cell immunity to SARS-CoV-2 is contributed by TCRs that recognize common viral antigens such as Influenza and CMV, even though the viral epitopes lack sequence identity to the SARS-CoV-2 epitopes. This finding is in contrast to multiple published studies in which pre-existing T-cell immunity is suggested to arise from shared epitopes between SARS-CoV-2 and other common cold-causing coronaviruses. However, our findings suggest that SARS-CoV-2 reactive T-cells are likely to be present in many individuals because of prior exposure to flu and CMV viruses.Swapnil MahajanVasumathi KodeKeshav BhojakCoral KarunakaranKayla LeeMalini ManoharanAthulya RameshSudheendra HVAnkita SrivastavaRekha SathianTahira KhanPrasanna KumarRavi GuptaPapia ChakrabortyAmitabha ChaudhuriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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Medicine R Science Q |
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Medicine R Science Q Swapnil Mahajan Vasumathi Kode Keshav Bhojak Coral Karunakaran Kayla Lee Malini Manoharan Athulya Ramesh Sudheendra HV Ankita Srivastava Rekha Sathian Tahira Khan Prasanna Kumar Ravi Gupta Papia Chakraborty Amitabha Chaudhuri Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals |
| description |
Abstract The COVID-19 pandemic has revealed a range of disease phenotypes in infected patients with asymptomatic, mild, or severe clinical outcomes, but the mechanisms that determine such variable outcomes remain unresolved. In this study, we identified immunodominant CD8 T-cell epitopes in the spike antigen using a novel TCR-binding algorithm. The predicted epitopes induced robust T-cell activation in unexposed donors demonstrating pre-existing CD4 and CD8 T-cell immunity to SARS-CoV-2 antigen. The T-cell reactivity to the predicted epitopes was higher than the Spike-S1 and S2 peptide pools in the unexposed donors. A key finding of our study is that pre-existing T-cell immunity to SARS-CoV-2 is contributed by TCRs that recognize common viral antigens such as Influenza and CMV, even though the viral epitopes lack sequence identity to the SARS-CoV-2 epitopes. This finding is in contrast to multiple published studies in which pre-existing T-cell immunity is suggested to arise from shared epitopes between SARS-CoV-2 and other common cold-causing coronaviruses. However, our findings suggest that SARS-CoV-2 reactive T-cells are likely to be present in many individuals because of prior exposure to flu and CMV viruses. |
| format |
article |
| author |
Swapnil Mahajan Vasumathi Kode Keshav Bhojak Coral Karunakaran Kayla Lee Malini Manoharan Athulya Ramesh Sudheendra HV Ankita Srivastava Rekha Sathian Tahira Khan Prasanna Kumar Ravi Gupta Papia Chakraborty Amitabha Chaudhuri |
| author_facet |
Swapnil Mahajan Vasumathi Kode Keshav Bhojak Coral Karunakaran Kayla Lee Malini Manoharan Athulya Ramesh Sudheendra HV Ankita Srivastava Rekha Sathian Tahira Khan Prasanna Kumar Ravi Gupta Papia Chakraborty Amitabha Chaudhuri |
| author_sort |
Swapnil Mahajan |
| title |
Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals |
| title_short |
Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals |
| title_full |
Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals |
| title_fullStr |
Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals |
| title_full_unstemmed |
Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals |
| title_sort |
immunodominant t-cell epitopes from the sars-cov-2 spike antigen reveal robust pre-existing t-cell immunity in unexposed individuals |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/0e59e27035f7492798884ba134ab486f |
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