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COVID-19 Patients Form Memory CD8+ T Cells that Recognize a Small Set of Shared Immunodominant Epitopes in SARS-CoV-2

51 Pages Posted: 11 Aug 2020 Publication Status: Review Complete

See all articles by Andrew P. Ferretti

Andrew P. Ferretti

TScan Therapeutics

Tomasz Kula

TScan Therapeutics

Yifan Wang

TScan Therapeutics

Dalena M.V. Nguyen

TScan Therapeutics

Adam Weinheimer

TScan Therapeutics

Garrett S. Dunlap

TScan Therapeutics

Qikai Xu

TScan Therapeutics

Nancy Nabilsi

TScan Therapeutics

Candace R. Perullo

TScan Therapeutics

Alexander W. Cristofaro

TScan Therapeutics

Holly J. Whitton

TScan Therapeutics

Amy Virbasius

TScan Therapeutics

Kenneth J. Olivier

TScan Therapeutics

Lyndsey R. Buckner

Ochsner Medical Center

Angela T. Alistar

Atlantic Health System

eric whitman

Atlantic Health System

Sarah A. Bertino

TScan Therapeutics

Shrikanta Chattopadhyay

TScan Therapeutics

Gavin MacBeath

TScan Therapeutics

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Abstract

Development of effective strategies to detect, treat, or prevent COVID-19 requires a robust understanding of natural immunity to SARS-CoV-2, including the cellular response mediated by T cells. We used an unbiased, genome-wide screening technology to comprehensively identify the specific epitopes in SARS-CoV-2 that are recognized by the memory CD8+ T cells of 25 COVID-19 convalescent patients. For each of six HLA types examined, patient T cells recognized 3–8 immunodominant epitopes that are broadly shared among patients, and single-cell sequencing revealed common structural features of TCRs recognizing these epitopes. We detected minimal cross-reactivity to the endemic coronaviruses that cause the common cold, arguing that pre-existing immunity to other coronaviruses does not significantly shape CD8+ T cell responses to SARS-CoV-2. Notably, only 3 of the 29 immunodominant epitopes we identified reside in the Spike protein, highlighting the need for second-generation vaccines that recapitulate natural CD8+ T cell immunity to SARS-CoV-2.

Funding: This work was supported by TScan Therapeutics, a privately-owned biotechnology company.

Ethical Approval: The study was conducted in accordance with the Declaration of Helsinki (1996), approved by the Atlantic Health System Institutional Review Board and the Ochsner Clinic Foundation Institutional Review Board and registered at clinicaltrials.gov (# NCT04397900).

Keywords: COVID-19, SARS-CoV-2, Coronavirus, CD8+ T cell, Unbiased, genome-wide screen, Immunodominant epitopes, vaccine design, T cell diagnostics, TCR therapeutics

Suggested Citation

Ferretti, Andrew P. and Kula, Tomasz and Wang, Yifan and Nguyen, Dalena M.V. and Weinheimer, Adam and Dunlap, Garrett S. and Xu, Qikai and Nabilsi, Nancy and Perullo, Candace R. and Cristofaro, Alexander W. and Whitton, Holly J. and Virbasius, Amy and Olivier, Kenneth J. and Buckner, Lyndsey R. and Alistar, Angela T. and whitman, eric and Bertino, Sarah A. and Chattopadhyay, Shrikanta and MacBeath, Gavin, COVID-19 Patients Form Memory CD8+ T Cells that Recognize a Small Set of Shared Immunodominant Epitopes in SARS-CoV-2. Available at SSRN: https://ssrn.com/abstract=3669387 or http://dx.doi.org/10.2139/ssrn.3669387
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Andrew P. Ferretti

TScan Therapeutics ( email )

United States

Tomasz Kula

TScan Therapeutics ( email )

United States

Yifan Wang

TScan Therapeutics

United States

Dalena M.V. Nguyen

TScan Therapeutics ( email )

United States

Adam Weinheimer

TScan Therapeutics ( email )

United States

Garrett S. Dunlap

TScan Therapeutics ( email )

United States

Qikai Xu

TScan Therapeutics ( email )

United States

Nancy Nabilsi

TScan Therapeutics ( email )

United States

Candace R. Perullo

TScan Therapeutics ( email )

United States

Alexander W. Cristofaro

TScan Therapeutics ( email )

United States

Holly J. Whitton

TScan Therapeutics ( email )

United States

Amy Virbasius

TScan Therapeutics ( email )

United States

Kenneth J. Olivier

TScan Therapeutics ( email )

United States

Lyndsey R. Buckner

Ochsner Medical Center ( email )

Angela T. Alistar

Atlantic Health System ( email )

Eric Whitman

Atlantic Health System ( email )

Sarah A. Bertino

TScan Therapeutics ( email )

United States

Shrikanta Chattopadhyay

TScan Therapeutics ( email )

United States

Gavin MacBeath (Contact Author)

TScan Therapeutics ( email )

United States

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