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Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’

Author

Listed:
  • David S. Fischer

    (Helmholtz Zentrum München, Neuherberg
    TUM School of Life Sciences Weihenstephan, Technical University of Munich)

  • Meshal Ansari

    (Helmholtz Zentrum München, Neuherberg
    Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL))

  • Karolin I. Wagner

    (Immunology and Hygiene, Technische Universität München (TUM))

  • Sebastian Jarosch

    (Immunology and Hygiene, Technische Universität München (TUM))

  • Yiqi Huang

    (Technische Universität München (TUM))

  • Christoph H. Mayr

    (Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL))

  • Maximilian Strunz

    (Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL))

  • Niklas J. Lang

    (Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL))

  • Elvira D’Ippolito

    (Immunology and Hygiene, Technische Universität München (TUM))

  • Monika Hammel

    (Immunology and Hygiene, Technische Universität München (TUM))

  • Laura Mateyka

    (Immunology and Hygiene, Technische Universität München (TUM))

  • Simone Weber

    (Immunology and Hygiene, Technische Universität München (TUM))

  • Lisa S. Wolff

    (Technische Universität München (TUM))

  • Klaus Witter

    (Cell Therapeutic Agents and Hemostaseology, LMU Munich
    University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for lung research (DZL))

  • Isis E. Fernandez

    (University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for lung research (DZL))

  • Gabriela Leuschner

    (University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for lung research (DZL))

  • Katrin Milger

    (University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for lung research (DZL))

  • Marion Frankenberger

    (Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL)
    Ludwig-Maximilians-University of Munich (LMU) and Asklepios Lung Clinic Munich-Gauting, Munich and Gauting)

  • Lorenz Nowak

    (Ludwig-Maximilians-University of Munich (LMU) and Asklepios Lung Clinic Munich-Gauting, Munich and Gauting)

  • Katharina Heinig-Menhard

    (Ludwig-Maximilians-University of Munich (LMU) and Asklepios Lung Clinic Munich-Gauting, Munich and Gauting)

  • Ina Koch

    (Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL)
    Asklepios Biobank for pulmonary diseases
    Member of the German Center for Lung Research (DZL), Center for Comprehensive Developmental Care (CDeCLMU), Department of Neonatology, Perinatal Center)

  • Mircea G. Stoleriu

    (Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL)
    Asklepios Biobank for pulmonary diseases
    Member of the German Center for Lung Research (DZL), Center for Comprehensive Developmental Care (CDeCLMU), Department of Neonatology, Perinatal Center)

  • Anne Hilgendorff

    (Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL)
    German Center for Infection Research (DZIF), partner site Munich)

  • Jürgen Behr

    (University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for lung research (DZL)
    Ludwig-Maximilians-University of Munich (LMU) and Asklepios Lung Clinic Munich-Gauting, Munich and Gauting)

  • Andreas Pichlmair

    (Technische Universität München (TUM)
    Technical University of Munich)

  • Benjamin Schubert

    (Helmholtz Zentrum München, Neuherberg
    Institute for Advanced Study, TUM)

  • Fabian J. Theis

    (Helmholtz Zentrum München, Neuherberg
    Institute for Advanced Study, TUM)

  • Dirk H. Busch

    (Immunology and Hygiene, Technische Universität München (TUM)
    Technical University of Munich
    Grosshadern, Hospital of the Ludwig-Maximilians University (LMU))

  • Herbert B. Schiller

    (Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL)
    Helmholtz Zentrum München, Neuherberg)

  • Kilian Schober

    (Immunology and Hygiene, Technische Universität München (TUM)
    Immunology and Hygiene, University Hospital of Erlangen)

Abstract

The in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we use single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients. To do so, we induce transcriptional shifts by antigenic stimulation in vitro and take advantage of natural T cell receptor (TCR) sequences of clonally expanded T cells as barcodes for ‘reverse phenotyping’. This allows identification of SARS-CoV-2-reactive TCRs and reveals phenotypic effects introduced by antigen-specific stimulation. We characterize transcriptional signatures of currently and previously activated SARS-CoV-2-reactive T cells, and show correspondence with phenotypes of T cells from the respiratory tract of patients with severe disease in the presence or absence of virus in independent cohorts. Reverse phenotyping is a powerful tool to provide an integrated insight into cellular states of SARS-CoV-2-reactive T cells across tissues and activation states.

Suggested Citation

  • David S. Fischer & Meshal Ansari & Karolin I. Wagner & Sebastian Jarosch & Yiqi Huang & Christoph H. Mayr & Maximilian Strunz & Niklas J. Lang & Elvira D’Ippolito & Monika Hammel & Laura Mateyka & Sim, 2021. "Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24730-4
    DOI: 10.1038/s41467-021-24730-4
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    Cited by:

    1. Tabea M. Eser & Olga Baranov & Manuel Huth & Mohammed I. M. Ahmed & Flora Deák & Kathrin Held & Luming Lin & Kami Pekayvaz & Alexander Leunig & Leo Nicolai & Georgios Pollakis & Marcus Buggert & David, 2023. "Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Felix Drost & Yang An & Irene Bonafonte-Pardàs & Lisa M. Dratva & Rik G. H. Lindeboom & Muzlifah Haniffa & Sarah A. Teichmann & Fabian Theis & Mohammad Lotfollahi & Benjamin Schubert, 2024. "Multi-modal generative modeling for joint analysis of single-cell T cell receptor and gene expression data," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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