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Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through 'reverse phenotyping'.
Fischer, David S; Ansari, Meshal; Wagner, Karolin I; Jarosch, Sebastian; Huang, Yiqi; Mayr, Christoph H; Strunz, Maximilian; Lang, Niklas J; D'Ippolito, Elvira; Hammel, Monika; Mateyka, Laura; Weber, Simone; Wolff, Lisa S; Witter, Klaus; Fernandez, Isis E; Leuschner, Gabriela; Milger, Katrin; Frankenberger, Marion; Nowak, Lorenz; Heinig-Menhard, Katharina; Koch, Ina; Stoleriu, Mircea G; Hilgendorff, Anne; Behr, Jürgen; Pichlmair, Andreas; Schubert, Benjamin; Theis, Fabian J; Busch, Dirk H; Schiller, Herbert B; Schober, Kilian.
  • Fischer DS; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, München, Germany.
  • Ansari M; TUM School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
  • Wagner KI; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, München, Germany.
  • Jarosch S; Institute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
  • Huang Y; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Mayr CH; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Strunz M; Institute of Virology, Technische Universität München (TUM), Munich, Germany.
  • Lang NJ; Institute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
  • D'Ippolito E; Institute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
  • Hammel M; Institute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
  • Mateyka L; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Weber S; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Wolff LS; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Witter K; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Fernandez IE; Institute of Virology, Technische Universität München (TUM), Munich, Germany.
  • Leuschner G; Laboratory of Immunogenetics and Molecular Diagnostics, Department of Transfusion Medicine, Cell Therapeutic Agents and Hemostaseology, LMU Munich, Munich, Germany.
  • Milger K; Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for lung research (DZL), Munich, Germany.
  • Frankenberger M; Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for lung research (DZL), Munich, Germany.
  • Nowak L; Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for lung research (DZL), Munich, Germany.
  • Heinig-Menhard K; Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for lung research (DZL), Munich, Germany.
  • Koch I; Institute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
  • Stoleriu MG; Center for Thoracic Surgery Munich, Ludwig-Maximilians-University of Munich (LMU) and Asklepios Lung Clinic Munich-Gauting, Munich and Gauting, Munich, Germany.
  • Hilgendorff A; Center for Thoracic Surgery Munich, Ludwig-Maximilians-University of Munich (LMU) and Asklepios Lung Clinic Munich-Gauting, Munich and Gauting, Munich, Germany.
  • Behr J; Center for Thoracic Surgery Munich, Ludwig-Maximilians-University of Munich (LMU) and Asklepios Lung Clinic Munich-Gauting, Munich and Gauting, Munich, Germany.
  • Pichlmair A; Institute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
  • Schubert B; Asklepios Biobank for pulmonary diseases, Gauting, Germany.
  • Theis FJ; Member of the German Center for Lung Research (DZL), Center for Comprehensive Developmental Care (CDeCLMU), Department of Neonatology, Perinatal Center, Munich, Germany.
  • Busch DH; Institute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
  • Schiller HB; Asklepios Biobank for pulmonary diseases, Gauting, Germany.
  • Schober K; Member of the German Center for Lung Research (DZL), Center for Comprehensive Developmental Care (CDeCLMU), Department of Neonatology, Perinatal Center, Munich, Germany.
Nat Commun ; 12(1): 4515, 2021 07 26.
Article in English | MEDLINE | ID: covidwho-1327196
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes / Sequence Analysis, RNA / Gene Expression Profiling / Single-Cell Analysis / COVID-19 Type of study: Etiology study / Incidence study / Observational study / Prognostic study / Risk factors Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-24730-4

Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes / Sequence Analysis, RNA / Gene Expression Profiling / Single-Cell Analysis / COVID-19 Type of study: Etiology study / Incidence study / Observational study / Prognostic study / Risk factors Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-24730-4