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SARS-CoV-2 infection establishes a stable and age-independent CD8+ T cell response against a dominant nucleocapsid epitope using restricted T cell receptors

Author

Listed:
  • Cecily Choy

    (National Institute on Aging, NIH)

  • Joseph Chen

    (National Institute on Aging, NIH)

  • Jiangyuan Li

    (National Institute on Aging, NIH)

  • D. Travis Gallagher

    (National Institute of Standards and Technology (NIST))

  • Jian Lu

    (National Institute on Aging, NIH)

  • Daichao Wu

    (University of Maryland Institute for Bioscience and Biotechnology Research)

  • Ainslee Zou

    (National Institute on Aging, NIH)

  • Humza Hemani

    (National Institute on Aging, NIH)

  • Beverly A. Baptiste

    (National Institute on Aging, NIH)

  • Emily Wichmann

    (National Institute on Aging, NIH)

  • Qian Yang

    (National Institute on Aging, NIH)

  • Jeffrey Ciffelo

    (National Institute on Aging, NIH)

  • Rui Yin

    (University of Maryland Institute for Bioscience and Biotechnology Research)

  • Julia McKelvy

    (National Institute on Aging, NIH)

  • Denise Melvin

    (National Institute on Aging, NIH)

  • Tonya Wallace

    (National Institute on Aging, NIH)

  • Christopher Dunn

    (National Institute on Aging, NIH)

  • Cuong Nguyen

    (National Institute on Aging, NIH)

  • Chee W. Chia

    (National Institute on Aging, NIH)

  • Jinshui Fan

    (National Institute on Aging, NIH)

  • Jeannie Ruffolo

    (National Institute on Aging, NIH)

  • Linda Zukley

    (National Institute on Aging, NIH)

  • Guixin Shi

    (Diagnologix LLC)

  • Tomokazu Amano

    (Elixirgen Therapeutics, Inc)

  • Yang An

    (National Institute on Aging, NIH)

  • Osorio Meirelles

    (National Institute on Aging, NIH)

  • Wells W. Wu

    (Facility for Biotechnology Resources, CBER, Food and Drug Administration)

  • Chao-Kai Chou

    (Facility for Biotechnology Resources, CBER, Food and Drug Administration)

  • Rong-Fong Shen

    (Facility for Biotechnology Resources, CBER, Food and Drug Administration)

  • Richard A. Willis

    (NIH Tetramer Core Facility at Emory University)

  • Minoru S. H. Ko

    (Elixirgen Therapeutics, Inc)

  • Yu-Tsueng Liu

    (Diagnologix LLC)

  • Supriyo De

    (National Institute on Aging, NIH)

  • Brian G. Pierce

    (University of Maryland Institute for Bioscience and Biotechnology Research)

  • Luigi Ferrucci

    (National Institute on Aging, NIH)

  • Josephine Egan

    (National Institute on Aging, NIH)

  • Roy Mariuzza

    (University of Maryland Institute for Bioscience and Biotechnology Research)

  • Nan-Ping Weng

    (National Institute on Aging, NIH)

Abstract

The resolution of SARS-CoV-2 replication hinges on cell-mediated immunity, wherein CD8+ T cells play a vital role. Nonetheless, the characterization of the specificity and TCR composition of CD8+ T cells targeting non-spike protein of SARS-CoV-2 before and after infection remains incomplete. Here, we analyzed CD8+ T cells recognizing six epitopes from the SARS-CoV-2 nucleocapsid (N) protein and found that SARS-CoV-2 infection slightly increased the frequencies of N-recognizing CD8+ T cells but significantly enhanced activation-induced proliferation compared to that of the uninfected donors. The frequencies of N-specific CD8+ T cells and their proliferative response to stimulation did not decrease over one year. We identified the N222-230 peptide (LLLDRLNQL, referred to as LLL thereafter) as a dominant epitope that elicited the greatest proliferative response from both convalescent and uninfected donors. Single-cell sequencing of T cell receptors (TCR) from LLL-specific CD8+ T cells revealed highly restricted Vα gene usage (TRAV12-2) with limited CDR3α motifs, supported by structural characterization of the TCR–LLL–HLA-A2 complex. Lastly, transcriptome analysis of LLL-specific CD8+ T cells from donors who had expansion (expanders) or no expansion (non-expanders) after in vitro stimulation identified increased chromatin modification and innate immune functions of CD8+ T cells in non-expanders. These results suggests that SARS-CoV-2 infection induces LLL-specific CD8+ T cell responses with a restricted TCR repertoire.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42430-z
    DOI: 10.1038/s41467-023-42430-z
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    References listed on IDEAS

    as
    1. Jonas S. Heitmann & Tatjana Bilich & Claudia Tandler & Annika Nelde & Yacine Maringer & Maddalena Marconato & Julia Reusch & Simon Jäger & Monika Denk & Marion Richter & Leonard Anton & Lisa Marie Web, 2022. "A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity," Nature, Nature, vol. 601(7894), pages 617-622, January.
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    Cited by:

    1. Jing Hu & Mingyao Pan & Brett Reid & Shelley Tworoger & Bo Li, 2024. "Quantifiable blood TCR repertoire components associate with immune aging," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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