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Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors

Author

Listed:
  • Daichao Wu

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of South China
    University of Maryland)

  • Alexander Kolesnikov

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of Maryland)

  • Rui Yin

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of Maryland)

  • Johnathan D. Guest

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of Maryland)

  • Ragul Gowthaman

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of Maryland)

  • Anton Shmelev

    (National Research Center for Hematology)

  • Yana Serdyuk

    (National Research Center for Hematology)

  • Dmitry V. Dianov

    (National Research Center for Hematology)

  • Grigory A. Efimov

    (National Research Center for Hematology)

  • Brian G. Pierce

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of Maryland)

  • Roy A. Mariuzza

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of Maryland)

Abstract

T cells play a vital role in combatting SARS-CoV-2 and forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS-CoV-2, such information on SARS-CoV-2-specific T-cell receptors (TCRs) bound to their peptide–MHC targets is lacking. Here we determine the structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ). The structures reveal the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of the TCRs to recognize natural variants of RLQ but not YLQ. Neither TCR recognizes homologous epitopes from human seasonal coronaviruses. By elucidating the mechanism for TCR recognition of an immunodominant yet variable epitope (YLQ) and a conserved but less commonly targeted epitope (RLQ), this study can inform prospective efforts to design vaccines to elicit pan-coronavirus immunity.

Suggested Citation

  • Daichao Wu & Alexander Kolesnikov & Rui Yin & Johnathan D. Guest & Ragul Gowthaman & Anton Shmelev & Yana Serdyuk & Dmitry V. Dianov & Grigory A. Efimov & Brian G. Pierce & Roy A. Mariuzza, 2022. "Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27669-8
    DOI: 10.1038/s41467-021-27669-8
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    References listed on IDEAS

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    1. Ugur Sahin & Alexander Muik & Isabel Vogler & Evelyna Derhovanessian & Lena M. Kranz & Mathias Vormehr & Jasmin Quandt & Nicole Bidmon & Alexander Ulges & Alina Baum & Kristen E. Pascal & Daniel Mauru, 2021. "BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans," Nature, Nature, vol. 595(7868), pages 572-577, July.
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    Cited by:

    1. Cecily Choy & Joseph Chen & Jiangyuan Li & D. Travis Gallagher & Jian Lu & Daichao Wu & Ainslee Zou & Humza Hemani & Beverly A. Baptiste & Emily Wichmann & Qian Yang & Jeffrey Ciffelo & Rui Yin & Juli, 2023. "SARS-CoV-2 infection establishes a stable and age-independent CD8+ T cell response against a dominant nucleocapsid epitope using restricted T cell receptors," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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