Title Unbiased Screens Show CD8(+) T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein.
Author Ferretti, Andrew P; Kula, Tomasz; Wang, Yifan; Nguyen, Dalena M V; Weinheimer, Adam; Dunlap, Garrett S; Xu, Qikai; Nabilsi, Nancy; Perullo, Candace R; Cristofaro, Alexander W; Whitton, Holly J; Virbasius, Amy; Olivier, Kenneth J Jr; Buckner, Lyndsey R; Alistar, Angela T; Whitman, Eric D; Bertino, Sarah A; Chattopadhyay, Shrikanta; MacBeath, Gavin
Journal Immunity Publication Year/Month 2020-Nov
PMID 33128877 PMCID PMC7574860
Affiliation + expend 1.TScan Therapeutics, Waltham, MA 02451, USA.

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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