Recruitment of highly cytotoxic CD8 T cell receptors in mild SARS-CoV-2 infection.
Karolin I Wagner, Laura M Mateyka, Sebastian Jarosch, Vincent Grass, Simone Weber, Kilian Schober, Monika Hammel, Teresa Burrell, Behnam Kalali, Holger Poppert, Henriette Beyer, Sophia Schambeck, Stefan Holdenrieder, Andrea Strötges-Achatz, Verena Haselmann, Michael Neumaier, Johanna Erber, Alina Priller, Sarah Yazici, Hedwig Roggendorf, Marcus Odendahl, Torsten Tonn, Andrea Dick, Klaus Witter, Hrvoje Mijočević, Ulrike Protzer, Percy A Knolle, Andreas Pichlmair, Claudia S Crowell, Markus Gerhard, Elvira D'Ippolito, Dirk H Busch
Author Information
Karolin I Wagner: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany.
Laura M Mateyka: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany.
Sebastian Jarosch: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany.
Vincent Grass: Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Simone Weber: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany.
Kilian Schober: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany.
Monika Hammel: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany.
Teresa Burrell: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany.
Behnam Kalali: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany.
Holger Poppert: Department of Neurology, Helios Klinikum München West, 81241 Munich, Germany; Neurologische Klinik, University Hospital Rechts der Isar, Technical University of Munich (TUM), 81675 Munich, Germany.
Henriette Beyer: Department of Neurology, Helios Klinikum München West, 81241 Munich, Germany.
Sophia Schambeck: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany; Department of Neurology, Helios Klinikum München West, 81241 Munich, Germany.
Stefan Holdenrieder: Institute of Laboratory Medicine, Munich Biomarker Research Center, Deutsches Herzzentrum München, Technical University of Munich (TUM), 80636 Munich, Germany.
Andrea Strötges-Achatz: Institute of Laboratory Medicine, Munich Biomarker Research Center, Deutsches Herzzentrum München, Technical University of Munich (TUM), 80636 Munich, Germany.
Verena Haselmann: Department of Clinical Chemistry, University Medicine Mannheim, Medical Faculty Mannheim of the University of Heidelberg, 68167 Mannheim, Germany.
Michael Neumaier: Department of Clinical Chemistry, University Medicine Mannheim, Medical Faculty Mannheim of the University of Heidelberg, 68167 Mannheim, Germany.
Johanna Erber: Department of Internal Medicine II, University Hospital rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany.
Alina Priller: Institute of Molecular Immunology and Experimental Oncology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Sarah Yazici: Institute of Molecular Immunology and Experimental Oncology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Hedwig Roggendorf: Institute of Molecular Immunology and Experimental Oncology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Marcus Odendahl: Experimental Transfusion Medicine, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany; Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, 01307 Dresden, Germany.
Torsten Tonn: Experimental Transfusion Medicine, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany; Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, 01307 Dresden, Germany.
Andrea Dick: Laboratory of Immunogenetics and Molecular Diagnostics, Department of Transfusion Medicine, Cellular Therapeutics and Hemostaseology, LMU University Hospital, 81377 Munich, Germany.
Klaus Witter: Laboratory of Immunogenetics and Molecular Diagnostics, Department of Transfusion Medicine, Cellular Therapeutics and Hemostaseology, LMU University Hospital, 81377 Munich, Germany.
Hrvoje Mijočević: Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Ulrike Protzer: Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
Percy A Knolle: Institute of Molecular Immunology and Experimental Oncology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
Andreas Pichlmair: Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
Claudia S Crowell: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
Markus Gerhard: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
Elvira D'Ippolito: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany. Electronic address: elvira.dippolito@tum.de.
Dirk H Busch: Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), 81675 Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany. Electronic address: dirk.busch@tum.de.
T cell immunity is crucial for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been studied widely on a quantitative level. However, the quality of responses, in particular of CD8 T cells, has only been investigated marginally so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common human Leukocyte antigen (HLA) class I molecules in convalescent individuals. SARS-CoV-2-specific CD8 T cells are detected up to 12 months after infection. TCR repertoires are diverse, with heterogeneous functional avidity and cytotoxicity toward virus-infected cells, as demonstrated for TCR-engineered T cells. High TCR functionality correlates with gene signatures that, remarkably, could be retrieved for each epitope:HLA combination analyzed. Overall, our data demonstrate that polyclonal and highly functional CD8 TCRs-classic features of protective immunity-are recruited upon mild SARS-CoV-2 infection, providing tools to assess the quality of and potentially restore functional CD8 T cell immunity.
