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Plate IV.281 · Publications

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

Article in Nature Communications, 26 July 2021.

Open accessLung, Epithelial Cells

  1. David S. Fischer
  2. Meshal Ansari
  3. Karolin I. Wagner
  4. Sebastian Jarosch
  5. Yiqi Huang
  6. Christoph H. Mayr
  7. Maximilian Strunz
  8. Niklas J. Lang
  9. Elvira D’Ippolito
  10. Monika Hammel
  11. Laura Mateyka
  12. Simone Weber
  13. Lisa S. Wolff
  14. Klaus Witter
  15. Isis E. Fernandez
  16. Gabriela Leuschner
  17. Katrin Milger
  18. Marion Frankenberger
  19. Lorenz Nowak
  20. Katharina Heinig-Menhard
  21. Ina Koch
  22. Mircea G. Stoleriu
  23. Anne Hilgendorff
  24. Jürgen Behr
  25. Andreas Pichlmair
  26. Benjamin Schubert
  27. Fabian J. Theis
  28. Dirk H. Busch
  29. Herbert B. Schiller
  30. Kilian Schober

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.

Versions2

  1. PublishedNature Communications10.1038/s41467-021-24730-4
  2. PreprintmedRxiv10.1101/2020.12.07.20245274

Cite

@article{fischer2021single,
  title = {{Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’}},
  author = {Fischer, David S. and Ansari, Meshal and Wagner, Karolin I. and Jarosch, Sebastian and Huang, Yiqi and Mayr, Christoph H. and Strunz, Maximilian and Lang, Niklas J. and D’Ippolito, Elvira and Hammel, Monika and Mateyka, Laura and Weber, Simone and Wolff, Lisa S. and Witter, Klaus and Fernandez, Isis E. and Leuschner, Gabriela and Milger, Katrin and Frankenberger, Marion and Nowak, Lorenz and Heinig-Menhard, Katharina and Koch, Ina and Stoleriu, Mircea G. and Hilgendorff, Anne and Behr, Jürgen and Pichlmair, Andreas and Schubert, Benjamin and Theis, Fabian J. and Busch, Dirk H. and Schiller, Herbert B. and Schober, Kilian},
  journal = {Nature Communications},
  publisher = {Springer Science and Business Media LLC},
  year = {2021},
  month = jul,
  doi = {10.1038/s41467-021-24730-4},
  url = {https://doi.org/10.1038/s41467-021-24730-4},
  pmid = {34312385},
  pmcid = {PMC8313584}
}
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