Unbiased Screens Show CD8 T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 That Largely Reside Outside the Spike Protein

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2020 Oct 31

PMID 33128877

Citations 209

Authors

Andrew P Ferretti

Tomasz Kula

Yifan Wang

Dalena M V Nguyen

Adam Weinheimer

Garrett S Dunlap

Qikai Xu

Nancy Nabilsi

Candace R Perullo

Alexander W Cristofaro

Holly J Whitton

Amy Virbasius

Kenneth J Olivier Jr

Lyndsey R Buckner

Angela T Alistar

Eric D Whitman

Sarah A Bertino

Shrikanta Chattopadhyay

Gavin MacBeath

Affiliations

Soon will be listed here.

Abstract

Developing effective strategies to prevent or treat coronavirus disease 2019 (COVID-19) requires understanding the natural immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used an unbiased, genome-wide screening technology to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8 T cells of COVID-19 patients. In total, we identified 3-8 epitopes for each of the 6 most prevalent human leukocyte antigen (HLA) types. These epitopes were broadly shared across patients and located in regions of the virus that are not subject to mutational variation. Notably, only 3 of the 29 shared epitopes were located in the spike protein, whereas most epitopes were located in ORF1ab or the nucleocapsid protein. We also found that CD8 T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold. Overall, these findings can inform development of next-generation vaccines that better recapitulate natural CD8 T cell immunity to SARS-CoV-2.

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