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

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

medRxiv, DOI: 10.1101/2020.12.07.20245274 (2021)
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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 used 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 induced transcriptional shifts by antigenic stimulation in vitro and took advantage of natural T cell receptor (TCR) sequences of clonally expanded T cells as barcodes for ‘reverse phenotyping’. This allowed identification of SARS-CoV-2-reactive TCRs and revealed phenotypic effects introduced by antigen-specific stimulation. We characterized transcriptional signatures of currently and previously activated SARS-CoV-2-reactive T cells, and showed 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.

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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Zeitschrift medRxiv
Begutachtungsstatus Peer reviewed
Förderungen Helmholtz AI