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SARS-CoV-2 Epitopes are Recognized by a Public and Diverse Repertoire of Human T-Cell Receptors

31 Pages Posted: 2 Jul 2020 Publication Status: Review Complete

See all articles by Alina S. Shomuradova

Alina S. Shomuradova

National Research Center for Hematology

Murad S. Vagida

National Research Center for Hematology

Savely A. Sheetikov

National Research Center for Hematology

Ksenia V. Zornikova

National Research Center for Hematology

Dmitry Kiryukhin

National Research Center for Hematology

Aleksei Titov

National Research Center for Hematology

Iuliia O. Peshkova

National Research Center for Hematology

Alexandra Khmelevskaya

National Research Center for Hematology

Dmitry V. Dianov

National Research Center for Hematology

Maria Malasheva

National Research Center for Hematology

Anton Shmelev

National Research Center for Hematology

Yana Serdyuk

National Research Center for Hematology

Dmitry V. Bagaev

Eindhoven University of Technology (TUE)

Anastasia Pivnyuk

Skolkovo Institute of Science and Technology - Center of Life Sciences

Dmitrii S. Shcherbinin

Pirogov Russian Medical State University

Alexandra V. Maleeva

National Research Center for Hematology

Naina T. Shakirova

National Research Center for Hematology

Artem Pilunov

National Research Center for Hematology

Dmitry B. Malko

National Research Center for Hematology

Ekaterina G. Khamaganova

National Research Center for Hematology

Bella Biderman

National Research Center for Hematology

Alexander Ivanov

Russian Academy of Sciences (RAS) - Center for Precision Genome Editing and Genetic Technologies for Biomedicine

Mikhail Shugay

Skolkovo Institute of Science and Technology - Center of Life Sciences

Grigory A. Efimov

National Research Center for Hematology

More...

Abstract

Understanding the hallmarks of the adaptive immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed the antibody and T-cell reactivity in COVID-19 convalescent patients and healthy donors sampled both prior to and during the pandemic. The numbers of SARS-CoV-2-specific T cells were increased in healthy donors examined during COVID-19. Combined with the absence of symptoms and humoral response across that group, this finding suggests that some individuals might be protected by T-cell cross-reactivity. In convalescent patients we observed public and diverse T-cell response to SARS-CoV-2 epitopes, revealing T-cell receptor motifs with germline-encoded features. Bulk CD4+ and CD8+ T-cell responses to Spike glycoprotein were mediated by groups of homologous T-cell receptors, some of them shared across multiple donors. Overall, our results demonstrate that T-cell response to SARS-CoV-2, including the identified set of specific T-cell receptors, can serve as a useful biomarker for surveying viral exposure and immunity.

Funding: Mikhail Shugay was supported by RFBR grant No 19-34-70011. Alexander Ivanov was supported by the Ministry of Science and Higher Education of the Russian Federation [Agreement No. 075-15-2019-1660].

Conflict of Interest: The authors declare no conflicts of interest.

Ethical Approval: All donors signed the informed consent approved by the National Research Center for Hematology ethical committee before the enrollment. Additionally, 10 healthy hematopoietic stem cell donor samples and 10 healthy donor serum samples were obtained from the blood bank with the approval of the local ethical committee.

Keywords: SARS-CoV-2, COVID-19, T-cell response, T-cell epitopes, T-cell receptor, TCR sequencing, clonal structure, MHC, HLA-A*02:01

Suggested Citation

Shomuradova, Alina S. and Vagida, Murad S. and Sheetikov, Savely A. and Zornikova, Ksenia V. and Kiryukhin, Dmitry and Titov, Aleksei and Peshkova, Iuliia O. and Khmelevskaya, Alexandra and Dianov, Dmitry V. and Malasheva, Maria and Shmelev, Anton and Serdyuk, Yana and Bagaev, Dmitry V. and Pivnyuk, Anastasia and Shcherbinin, Dmitrii S. and Maleeva, Alexandra V. and Shakirova, Naina T. and Pilunov, Artem and Malko, Dmitry B. and Khamaganova, Ekaterina G. and Biderman, Bella and Ivanov, Alexander and Shugay, Mikhail and Efimov, Grigory A., SARS-CoV-2 Epitopes are Recognized by a Public and Diverse Repertoire of Human T-Cell Receptors. Available at SSRN: https://ssrn.com/abstract=3640836
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Alina S. Shomuradova

National Research Center for Hematology ( email )

Russia

Murad S. Vagida

National Research Center for Hematology ( email )

Russia

Savely A. Sheetikov

National Research Center for Hematology ( email )

Russia

Ksenia V. Zornikova

National Research Center for Hematology ( email )

Russia

Dmitry Kiryukhin

National Research Center for Hematology ( email )

Russia

Aleksei Titov

National Research Center for Hematology ( email )

Russia

Iuliia O. Peshkova

National Research Center for Hematology ( email )

Russia

Alexandra Khmelevskaya

National Research Center for Hematology ( email )

Russia

Dmitry V. Dianov

National Research Center for Hematology ( email )

Russia

Maria Malasheva

National Research Center for Hematology ( email )

Russia

Anton Shmelev

National Research Center for Hematology ( email )

Russia

Yana Serdyuk

National Research Center for Hematology ( email )

Russia

Dmitry V. Bagaev

Eindhoven University of Technology (TUE) ( email )

PO Box 513
Eindhoven, 5600 MB
Netherlands

Anastasia Pivnyuk

Skolkovo Institute of Science and Technology - Center of Life Sciences ( email )

Novaya St., 100
Skolkovo, 143025
Russia

Dmitrii S. Shcherbinin

Pirogov Russian Medical State University ( email )

Ostrovityanova Street
Moscow, 117997
Russia

Alexandra V. Maleeva

National Research Center for Hematology ( email )

Russia

Naina T. Shakirova

National Research Center for Hematology ( email )

Russia

Artem Pilunov

National Research Center for Hematology ( email )

Russia

Dmitry B. Malko

National Research Center for Hematology ( email )

Russia

Ekaterina G. Khamaganova

National Research Center for Hematology ( email )

Russia

Bella Biderman

National Research Center for Hematology ( email )

Russia

Alexander Ivanov

Russian Academy of Sciences (RAS) - Center for Precision Genome Editing and Genetic Technologies for Biomedicine ( email )

Leninsky Ave, 14
Moscow, 119991
Russia

Mikhail Shugay

Skolkovo Institute of Science and Technology - Center of Life Sciences ( email )

Novaya St., 100
Skolkovo, 143025
Russia

Grigory A. Efimov (Contact Author)

National Research Center for Hematology ( email )

Russia

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