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

Autor:	Ferretti AP; TScan Therapeutics, Waltham, MA 02451, USA., Kula T; TScan Therapeutics, Waltham, MA 02451, USA., Wang Y; TScan Therapeutics, Waltham, MA 02451, USA., Nguyen DMV; TScan Therapeutics, Waltham, MA 02451, USA., Weinheimer A; TScan Therapeutics, Waltham, MA 02451, USA., Dunlap GS; TScan Therapeutics, Waltham, MA 02451, USA., Xu Q; TScan Therapeutics, Waltham, MA 02451, USA., Nabilsi N; TScan Therapeutics, Waltham, MA 02451, USA., Perullo CR; TScan Therapeutics, Waltham, MA 02451, USA., Cristofaro AW; TScan Therapeutics, Waltham, MA 02451, USA., Whitton HJ; TScan Therapeutics, Waltham, MA 02451, USA., Virbasius A; TScan Therapeutics, Waltham, MA 02451, USA., Olivier KJ Jr; TScan Therapeutics, Waltham, MA 02451, USA., Buckner LR; Ochsner Medical Center, New Orleans, LA 70121, USA., Alistar AT; Atlantic Health System, Morristown, NJ 07960, USA., Whitman ED; Atlantic Health System, Morristown, NJ 07960, USA., Bertino SA; TScan Therapeutics, Waltham, MA 02451, USA., Chattopadhyay S; TScan Therapeutics, Waltham, MA 02451, USA., MacBeath G; TScan Therapeutics, Waltham, MA 02451, USA. Electronic address: gmacbeath@tscan.com.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2020 Nov 17; Vol. 53 (5), pp. 1095-1107.e3. Date of Electronic Publication: 2020 Oct 20.
DOI:	10.1016/j.immuni.2020.10.006
Abstrakt:	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. Competing Interests: Declaration of Interests A.P.F., Y.W., D.M.V.N., A.W., G.S.D., Q.X., N.N., C.R.P., A.W.C., H.J.W., A.V., K.J.O., S.A.B., and G.M. are employees of TScan Therapeutics. T.K. is a founder of TScan Therapeutics, and T.K. and G.M. hold equity in TScan Therapeutics. S.C. is a consultant for TScan Therapeutics. A patent application relating to the T-Scan technology used in the current manuscript was filed previously by The Brigham and Women’s Hospital, Inc. Provisional patent applications covering SARS-CoV-2 epitope sequences and TCR sequences described in the current manuscript as well as related uses, diagnostics, therapeutics, and vaccines for COVID-19 were filed by TScan Therapeutics, Inc. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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