Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Fischer, DS; Ansari, M; Wagner, KI; Jarosch, S; Huang, Y; Mayr, CH; Strunz, M; Lang, NJ; D'Ippolito, E; Hammel, M; Mateyka, L; Weber, S; Wolff, LS; Witter, K; Fernandez, IE; Leuschner, G; Milger, K; Frankenberger, M; Nowak, L; Heinig-Menhard, K; Koch, I; Stoleriu, MG; Hilgendorff, A; Behr, J; Pichlmair, A; Schubert, B; Theis, FJ; Busch, DH; Schiller, HB; Schober, K.
Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through 'reverse phenotyping'.
Nat Commun. 2021; 12(1):4515
Doi: 10.1038/s41467-021-24730-4
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- Co-Autor*innen der Med Uni Graz
- Milger-Kneidinger Katrin
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- 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.
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- Aged - administration & dosage
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- CD4-Positive T-Lymphocytes - metabolism, virology
- COVID-19 - epidemiology, immunology, virology
- Cells, Cultured - administration & dosage
- Cohort Studies - administration & dosage
- Female - administration & dosage
- Gene Expression Profiling - methods
- Humans - administration & dosage
- Male - administration & dosage
- Middle Aged - administration & dosage
- Pandemics - administration & dosage
- Receptors, Antigen, T-Cell - genetics, immunology, metabolism
- SARS-CoV-2 - physiology
- Sequence Analysis, RNA - methods
- Single-Cell Analysis - methods
- T-Lymphocytes - metabolism, virology