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Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals

View ORCID ProfileSwapnil Mahajan, Vasumathi Kode, Keshav Bhojak, Coral M. Magdalene, Kayla Lee, View ORCID ProfileMalini Manoharan, Athulya Ramesh, HV Sudheendra, Ankita Srivastava, Rekha Sathian, Tahira Khan, Prasanna Kumar, Papia Chakraborty, View ORCID ProfileAmitabha Chaudhuri
doi: https://doi.org/10.1101/2020.11.03.367375
Swapnil Mahajan
1MedGenome, Bangalore, India
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  • ORCID record for Swapnil Mahajan
Vasumathi Kode
2MedGenome, Foster City, USA
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Keshav Bhojak
1MedGenome, Bangalore, India
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Coral M. Magdalene
1MedGenome, Bangalore, India
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Kayla Lee
2MedGenome, Foster City, USA
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Malini Manoharan
1MedGenome, Bangalore, India
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Athulya Ramesh
1MedGenome, Bangalore, India
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HV Sudheendra
1MedGenome, Bangalore, India
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Ankita Srivastava
1MedGenome, Bangalore, India
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Rekha Sathian
1MedGenome, Bangalore, India
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Tahira Khan
2MedGenome, Foster City, USA
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Prasanna Kumar
1MedGenome, Bangalore, India
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Papia Chakraborty
2MedGenome, Foster City, USA
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  • For correspondence: amitc@medgenome.com
Amitabha Chaudhuri
2MedGenome, Foster City, USA
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  • ORCID record for Amitabha Chaudhuri
  • For correspondence: amitc@medgenome.com
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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 RBD and the non-RBD domain of the spike antigen using a novel TCR-binding algorithm. A selected pool of 11 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 containing 157 and 158 peptides both in unexposed donors and in convalescent patients suggesting that strong T-cell epitopes are likely to be missed when larger peptide pools are used in assays. 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. Whether the presence of pre-existing T-cell immunity provides protection against COVID-19 or contributes to severe disease phenotype remains to be determined in a larger cohort. However, our findings raise the expectation that a significant majority of the global population is likely to have SARS-CoV-2 reactive T-cells because of prior exposure to flu and CMV viruses, in addition to common cold-causing coronaviruses.

Competing Interest Statement

All authors are employees of MedGenome.

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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. All rights reserved. No reuse allowed without permission.
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Posted November 05, 2020.
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Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals
Swapnil Mahajan, Vasumathi Kode, Keshav Bhojak, Coral M. Magdalene, Kayla Lee, Malini Manoharan, Athulya Ramesh, HV Sudheendra, Ankita Srivastava, Rekha Sathian, Tahira Khan, Prasanna Kumar, Papia Chakraborty, Amitabha Chaudhuri
bioRxiv 2020.11.03.367375; doi: https://doi.org/10.1101/2020.11.03.367375
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Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals
Swapnil Mahajan, Vasumathi Kode, Keshav Bhojak, Coral M. Magdalene, Kayla Lee, Malini Manoharan, Athulya Ramesh, HV Sudheendra, Ankita Srivastava, Rekha Sathian, Tahira Khan, Prasanna Kumar, Papia Chakraborty, Amitabha Chaudhuri
bioRxiv 2020.11.03.367375; doi: https://doi.org/10.1101/2020.11.03.367375

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