PMID- 33128877 OWN - NLM STAT- MEDLINE DCOM- 20201130 LR - 20231112 IS - 1097-4180 (Electronic) IS - 1074-7613 (Print) IS - 1074-7613 (Linking) VI - 53 IP - 5 DP - 2020 Nov 17 TI - Unbiased Screens Show CD8(+) T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein. PG - 1095-1107.e3 LID - S1074-7613(20)30447-7 [pii] LID - 10.1016/j.immuni.2020.10.006 [doi] AB - 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. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Ferretti, Andrew P AU - Ferretti AP AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Kula, Tomasz AU - Kula T AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Wang, Yifan AU - Wang Y AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Nguyen, Dalena M V AU - Nguyen DMV AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Weinheimer, Adam AU - Weinheimer A AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Dunlap, Garrett S AU - Dunlap GS AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Xu, Qikai AU - Xu Q AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Nabilsi, Nancy AU - Nabilsi N AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Perullo, Candace R AU - Perullo CR AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Cristofaro, Alexander W AU - Cristofaro AW AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Whitton, Holly J AU - Whitton HJ AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Virbasius, Amy AU - Virbasius A AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Olivier, Kenneth J Jr AU - Olivier KJ Jr AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Buckner, Lyndsey R AU - Buckner LR AD - Ochsner Medical Center, New Orleans, LA 70121, USA. FAU - Alistar, Angela T AU - Alistar AT AD - Atlantic Health System, Morristown, NJ 07960, USA. FAU - Whitman, Eric D AU - Whitman ED AD - Atlantic Health System, Morristown, NJ 07960, USA. FAU - Bertino, Sarah A AU - Bertino SA AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - Chattopadhyay, Shrikanta AU - Chattopadhyay S AD - TScan Therapeutics, Waltham, MA 02451, USA. FAU - MacBeath, Gavin AU - MacBeath G AD - TScan Therapeutics, Waltham, MA 02451, USA. Electronic address: gmacbeath@tscan.com. LA - eng PT - Journal Article DEP - 20201020 PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Coronavirus Nucleocapsid Proteins) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Immunodominant Epitopes) RN - 0 (Nucleocapsid Proteins) RN - 0 (ORF1ab polyprotein, SARS-CoV-2) RN - 0 (Phosphoproteins) RN - 0 (Polyproteins) RN - 0 (Spike Glycoprotein, Coronavirus) RN - 0 (Viral Proteins) RN - 0 (nucleocapsid phosphoprotein, SARS-CoV-2) RN - 0 (spike protein, SARS-CoV-2) SB - IM MH - Adult MH - Aged MH - Betacoronavirus/*immunology/isolation & purification MH - CD8-Positive T-Lymphocytes/*immunology MH - COVID-19 MH - Convalescence MH - Coronavirus/immunology MH - Coronavirus Infections/diagnosis/*immunology MH - Coronavirus Nucleocapsid Proteins MH - Epitope Mapping MH - Epitopes, T-Lymphocyte MH - Female MH - Humans MH - Immunodominant Epitopes MH - Immunologic Memory MH - Male MH - Middle Aged MH - Nucleocapsid Proteins/immunology MH - Pandemics MH - Phosphoproteins MH - Pneumonia, Viral/diagnosis/*immunology MH - Polyproteins MH - SARS-CoV-2 MH - Spike Glycoprotein, Coronavirus/*immunology MH - Viral Proteins/immunology MH - Young Adult PMC - PMC7574860 OTO - NOTNLM OT - CD8+ T cells OT - COVID-19 OT - SARS-CoV-2 OT - T-Scan OT - immunity OT - immunodominant epitopes OT - novel coronavirus OT - seasonal coronaviruses OT - spike protein OT - vaccine COIS- 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. EDAT- 2020/11/01 06:00 MHDA- 2020/12/01 06:00 PMCR- 2020/10/20 CRDT- 2020/10/31 20:07 PHST- 2020/07/31 00:00 [received] PHST- 2020/09/03 00:00 [revised] PHST- 2020/10/13 00:00 [accepted] PHST- 2020/11/01 06:00 [pubmed] PHST- 2020/12/01 06:00 [medline] PHST- 2020/10/31 20:07 [entrez] PHST- 2020/10/20 00:00 [pmc-release] AID - S1074-7613(20)30447-7 [pii] AID - 10.1016/j.immuni.2020.10.006 [doi] PST - ppublish SO - Immunity. 2020 Nov 17;53(5):1095-1107.e3. doi: 10.1016/j.immuni.2020.10.006. Epub 2020 Oct 20.