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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.
Immunity. 2020 11 17; 53(5):1095-1107.e3.I

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.

Authors+Show Affiliations

TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.Ochsner Medical Center, New Orleans, LA 70121, USA.Atlantic Health System, Morristown, NJ 07960, USA.Atlantic Health System, Morristown, NJ 07960, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA.TScan Therapeutics, Waltham, MA 02451, USA. Electronic address: gmacbeath@tscan.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33128877

Citation

Ferretti, Andrew P., et al. "Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 That Largely Reside Outside the Spike Protein." Immunity, vol. 53, no. 5, 2020, pp. 1095-1107.e3.
Ferretti AP, Kula T, Wang Y, et al. Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein. Immunity. 2020;53(5):1095-1107.e3.
Ferretti, A. P., Kula, T., Wang, Y., Nguyen, D. M. V., Weinheimer, A., Dunlap, G. S., Xu, Q., Nabilsi, N., Perullo, C. R., Cristofaro, A. W., Whitton, H. J., Virbasius, A., Olivier, K. J., Buckner, L. R., Alistar, A. T., Whitman, E. D., Bertino, S. A., Chattopadhyay, S., & MacBeath, G. (2020). Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein. Immunity, 53(5), 1095-e3. https://doi.org/10.1016/j.immuni.2020.10.006
Ferretti AP, et al. Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 That Largely Reside Outside the Spike Protein. Immunity. 2020 11 17;53(5):1095-1107.e3. PubMed PMID: 33128877.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein. AU - Ferretti,Andrew P, AU - Kula,Tomasz, AU - Wang,Yifan, AU - Nguyen,Dalena M V, AU - Weinheimer,Adam, AU - Dunlap,Garrett S, AU - Xu,Qikai, AU - Nabilsi,Nancy, AU - Perullo,Candace R, AU - Cristofaro,Alexander W, AU - Whitton,Holly J, AU - Virbasius,Amy, AU - Olivier,Kenneth J,Jr AU - Buckner,Lyndsey R, AU - Alistar,Angela T, AU - Whitman,Eric D, AU - Bertino,Sarah A, AU - Chattopadhyay,Shrikanta, AU - MacBeath,Gavin, Y1 - 2020/10/20/ PY - 2020/07/31/received PY - 2020/09/03/revised PY - 2020/10/13/accepted PY - 2020/11/1/pubmed PY - 2020/12/1/medline PY - 2020/10/31/entrez KW - CD8+ T cells KW - COVID-19 KW - SARS-CoV-2 KW - T-Scan KW - immunity KW - immunodominant epitopes KW - novel coronavirus KW - seasonal coronaviruses KW - spike protein KW - vaccine SP - 1095 EP - 1107.e3 JF - Immunity JO - Immunity VL - 53 IS - 5 N2 - 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. SN - 1097-4180 UR - https://www.unboundmedicine.com/medline/citation/33128877/Unbiased_Screens_Show_CD8+_T_Cells_of_COVID_19_Patients_Recognize_Shared_Epitopes_in_SARS_CoV_2_that_Largely_Reside_outside_the_Spike_Protein_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1074-7613(20)30447-7 DB - PRIME DP - Unbound Medicine ER -