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Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein.

Authors
  • Ferretti, Andrew P1
  • Kula, Tomasz1
  • Wang, Yifan1
  • Nguyen, Dalena M V1
  • Weinheimer, Adam1
  • Dunlap, Garrett S1
  • Xu, Qikai1
  • Nabilsi, Nancy1
  • Perullo, Candace R1
  • Cristofaro, Alexander W1
  • Whitton, Holly J1
  • Virbasius, Amy1
  • Olivier, Kenneth J Jr1
  • Buckner, Lyndsey R2
  • Alistar, Angela T3
  • Whitman, Eric D3
  • Bertino, Sarah A1
  • Chattopadhyay, Shrikanta1
  • MacBeath, Gavin4
  • 1 TScan Therapeutics, Waltham, MA 02451, USA.
  • 2 Ochsner Medical Center, New Orleans, LA 70121, USA.
  • 3 Atlantic Health System, Morristown, NJ 07960, USA.
  • 4 TScan Therapeutics, Waltham, MA 02451, USA. Electronic address: [email protected]
Type
Published Article
Journal
Immunity
Publication Date
Nov 17, 2020
Volume
53
Issue
5
Identifiers
DOI: 10.1016/j.immuni.2020.10.006
PMID: 33128877
Source
Medline
Keywords
Language
English
License
Unknown

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. Copyright © 2020 Elsevier Inc. All rights reserved.

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