tetano
Editor, Senior Moderator
Nat Commun
. 2021 Jul 26;12(1):4515.
doi: 10.1038/s41467-021-24730-4.
Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through 'reverse phenotyping'
David S Fischer[SUP] #[/SUP][SUP] 1 2 [/SUP], Meshal Ansari[SUP] #[/SUP][SUP] 1 3 [/SUP], Karolin I Wagner[SUP] #[/SUP][SUP] 4 [/SUP], Sebastian Jarosch[SUP] 4 [/SUP], Yiqi Huang[SUP] 5 [/SUP], Christoph H Mayr[SUP] 3 [/SUP], Maximilian Strunz[SUP] 3 [/SUP], Niklas J Lang[SUP] 3 [/SUP], Elvira D'Ippolito[SUP] 4 [/SUP], Monika Hammel[SUP] 4 [/SUP], Laura Mateyka[SUP] 4 [/SUP], Simone Weber[SUP] 4 [/SUP], Lisa S Wolff[SUP] 5 [/SUP], Klaus Witter[SUP] 6 7 [/SUP], Isis E Fernandez[SUP] 7 [/SUP], Gabriela Leuschner[SUP] 7 [/SUP], Katrin Milger[SUP] 7 [/SUP], Marion Frankenberger[SUP] 3 8 [/SUP], Lorenz Nowak[SUP] 8 [/SUP], Katharina Heinig-Menhard[SUP] 8 [/SUP], Ina Koch[SUP] 3 9 10 [/SUP], Mircea G Stoleriu[SUP] 3 9 10 [/SUP], Anne Hilgendorff[SUP] 3 11 [/SUP], Jürgen Behr[SUP] 7 8 [/SUP], Andreas Pichlmair[SUP] 5 12 [/SUP], Benjamin Schubert[SUP] 1 13 [/SUP], Fabian J Theis[SUP] 1 13 [/SUP], Dirk H Busch[SUP] 4 12 14 [/SUP], Herbert B Schiller[SUP] 15 16 [/SUP], Kilian Schober[SUP] 17 18 [/SUP]
Affiliations
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.
. 2021 Jul 26;12(1):4515.
doi: 10.1038/s41467-021-24730-4.
Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through 'reverse phenotyping'
David S Fischer[SUP] #[/SUP][SUP] 1 2 [/SUP], Meshal Ansari[SUP] #[/SUP][SUP] 1 3 [/SUP], Karolin I Wagner[SUP] #[/SUP][SUP] 4 [/SUP], Sebastian Jarosch[SUP] 4 [/SUP], Yiqi Huang[SUP] 5 [/SUP], Christoph H Mayr[SUP] 3 [/SUP], Maximilian Strunz[SUP] 3 [/SUP], Niklas J Lang[SUP] 3 [/SUP], Elvira D'Ippolito[SUP] 4 [/SUP], Monika Hammel[SUP] 4 [/SUP], Laura Mateyka[SUP] 4 [/SUP], Simone Weber[SUP] 4 [/SUP], Lisa S Wolff[SUP] 5 [/SUP], Klaus Witter[SUP] 6 7 [/SUP], Isis E Fernandez[SUP] 7 [/SUP], Gabriela Leuschner[SUP] 7 [/SUP], Katrin Milger[SUP] 7 [/SUP], Marion Frankenberger[SUP] 3 8 [/SUP], Lorenz Nowak[SUP] 8 [/SUP], Katharina Heinig-Menhard[SUP] 8 [/SUP], Ina Koch[SUP] 3 9 10 [/SUP], Mircea G Stoleriu[SUP] 3 9 10 [/SUP], Anne Hilgendorff[SUP] 3 11 [/SUP], Jürgen Behr[SUP] 7 8 [/SUP], Andreas Pichlmair[SUP] 5 12 [/SUP], Benjamin Schubert[SUP] 1 13 [/SUP], Fabian J Theis[SUP] 1 13 [/SUP], Dirk H Busch[SUP] 4 12 14 [/SUP], Herbert B Schiller[SUP] 15 16 [/SUP], Kilian Schober[SUP] 17 18 [/SUP]
Affiliations
- PMID: 34312385
- DOI: 10.1038/s41467-021-24730-4
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.