Single-Cell RNA Sequencing Reveals Ex Vivo Signatures of SARS-CoV-2-Reactive T Cells Through ‘Reverse Phenotyping’

MCML Authors

Fabian Theis

Prof. Dr.

Principal Investigator

Mathematical Modelling of Biological Systems

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.

article

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Nature Communications

12.1. Jul. 2021.

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Authors

D. S. Fischer • M. Ansari • K. I. Wagner • S. Jarosch • Y.  • C. H. Mayr • M. Lang • E. D’Ippolito • M. Hammel • L. Mateyka • S. Weber • L. S. Wolff • K. Witter • I. E. Fernandez • G. Leuschner • K. Milger • M. Frankenberger • L. Nowak • K. Heinig-Menhard • I. Koch • M. G. Stoleriu • A. Hilgendorff • J. Behr • A. Pichlmair • B. Schubert • F. J. Theis • D. H. Busch • H. B. Schiller • K. Schober

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Links

DOI

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Research Area

 C2 | Biology