Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease.
2020 Jun 30
a month ago
Publication Type
Journal Article
2020-Jun-30 / :
Schultheiß C 1, Paschold L 1, Simnica D 1, Mohme M 2, Willscher E 1, von Wenserski L 1, Scholz R 1, Wieters I 3, Dahlke C 4, Tolosa E 5, Sedding DG 6, Ciesek S 7, Addo M 4, Binder M 8
  • 2. Department of Neurosurgery, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany.
  • 3. Infectious Diseases, Department of Internal Medicine II, University Hospital Frankfurt, 60596 Frankfurt am Main, Germany.
  • 4. First Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Department for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.
  • 5. Department of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • 6. Mid-German Heart Center, Department of Cardiology and Intensive Care Medicine, University Hospital, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany.
  • 7. Institute of Medical Virology, University Hospital, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany; Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Branch Translational Medicine und Pharmacology, 60596 Frankfurt am Main, Germany; German Center for Infection Research (DZIF), External partner site Frankfurt, 60596 Frankfurt am Main, Germany.
  • 8. Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany. Electronic address: [email protected]
We profiled adaptive immunity in COVID-19 patients with active infection or after recovery and created a repository of currently >14 million B and T cell receptor (BCR and TCR) sequences from the blood of these patients. The B cell response showed converging IGHV3-driven BCR clusters closely associated with SARS-CoV-2 antibodies. Clonality and skewing of TCR repertoires were associated with interferon type I and III responses, early CD4+ and CD8+ T cell activation, and counterregulation by the co-receptors BTLA, Tim-3, PD-1, TIGIT, and CD73. Tfh, Th17-like, and nonconventional (but not classical antiviral) Th1 cell polarizations were induced. SARS-CoV-2-specific T cell responses were driven by TCR clusters shared between patients with a characteristic trajectory of clonotypes and traceability over the disease course. Our data provide fundamental insight into adaptive immunity to SARS-CoV-2 with the actively updated repository providing a resource for the scientific community urgently needed to inform therapeutic concepts and vaccine development.
Keywords: B cell repertoire COVID-19 SARS-CoV-2-specific antibody T cell compartments T cell receptor clusters T cell repertoire cytokine profile immunoglobulin heavy chain interferon
LocationUnited States

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