Cell Reports (Apr 2024)
Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation
- Marlies Boeren,
- Nicky de Vrij,
- My K. Ha,
- Sebastiaan Valkiers,
- Aisha Souquette,
- Sofie Gielis,
- Mariia Kuznetsova,
- Jolien Schippers,
- Esther Bartholomeus,
- Johan Van den Bergh,
- Nele Michels,
- Olivier Aerts,
- Julie Leysen,
- An Bervoets,
- Julien Lambert,
- Elke Leuridan,
- Johan Wens,
- Karin Peeters,
- Marie-Paule Emonds,
- George Elias,
- Niels Vandamme,
- Hilde Jansens,
- Wim Adriaensen,
- Arvid Suls,
- Stijn Vanhee,
- Niel Hens,
- Evelien Smits,
- Pierre Van Damme,
- Paul G. Thomas,
- Philippe Beutels,
- Peter Ponsaerts,
- Viggo Van Tendeloo,
- Peter Delputte,
- Kris Laukens,
- Pieter Meysman,
- Benson Ogunjimi
Affiliations
- Marlies Boeren
- Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium; Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Nicky de Vrij
- Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Adrem Data Lab, Department of Mathematics and Computer Science, University of Antwerp, Antwerp, Belgium; Biomedical Informatics Research Network Antwerp (biomina), University of Antwerp, Antwerp, Belgium; Clinical Immunology Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
- My K. Ha
- Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Sebastiaan Valkiers
- Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Adrem Data Lab, Department of Mathematics and Computer Science, University of Antwerp, Antwerp, Belgium; Biomedical Informatics Research Network Antwerp (biomina), University of Antwerp, Antwerp, Belgium
- Aisha Souquette
- Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA
- Sofie Gielis
- Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Adrem Data Lab, Department of Mathematics and Computer Science, University of Antwerp, Antwerp, Belgium; Biomedical Informatics Research Network Antwerp (biomina), University of Antwerp, Antwerp, Belgium
- Mariia Kuznetsova
- Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Jolien Schippers
- Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Esther Bartholomeus
- Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Johan Van den Bergh
- Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
- Nele Michels
- Department of Family Medicine and Population Health (FAMPOP), Center for General Practice/Family Medicine, University of Antwerp, Antwerp, Belgium
- Olivier Aerts
- Department of Dermatology, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium
- Julie Leysen
- Department of Dermatology, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium
- An Bervoets
- Department of Dermatology, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium
- Julien Lambert
- Department of Dermatology, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium
- Elke Leuridan
- Centre for the Evaluation of Vaccination (CEV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Johan Wens
- Department of Family Medicine and Population Health (FAMPOP), Center for General Practice/Family Medicine, University of Antwerp, Antwerp, Belgium
- Karin Peeters
- Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Marie-Paule Emonds
- Histocompatibility and Immunogenetic Laboratory, Rode Kruis-Vlaanderen, Mechelen, Belgium
- George Elias
- Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Niels Vandamme
- Data Mining and Modeling for Biomedicine Group, VIB-UGent Center for Inflammation Research, 9052 Ghent, Belgium; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium
- Hilde Jansens
- Department of Clinical Microbiology, Antwerp University Hospital, Antwerp, Belgium
- Wim Adriaensen
- Clinical Immunology Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
- Arvid Suls
- Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium
- Stijn Vanhee
- Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Department of Head and Skin, Ghent University, Ghent, Belgium
- Niel Hens
- Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; I-BioStat, Data Science Institute, Hasselt University, Hasselt, Belgium
- Evelien Smits
- Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium
- Pierre Van Damme
- Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Centre for the Evaluation of Vaccination (CEV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Paul G. Thomas
- Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA
- Philippe Beutels
- Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Peter Ponsaerts
- Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
- Viggo Van Tendeloo
- Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium
- Peter Delputte
- Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium
- Kris Laukens
- Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Adrem Data Lab, Department of Mathematics and Computer Science, University of Antwerp, Antwerp, Belgium; Biomedical Informatics Research Network Antwerp (biomina), University of Antwerp, Antwerp, Belgium
- Pieter Meysman
- Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Adrem Data Lab, Department of Mathematics and Computer Science, University of Antwerp, Antwerp, Belgium; Biomedical Informatics Research Network Antwerp (biomina), University of Antwerp, Antwerp, Belgium
- Benson Ogunjimi
- Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), Antwerp, Belgium; Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; Department of Paediatrics, Antwerp University Hospital, Antwerp, Belgium; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 4
p. 114062
Abstract
Summary: The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4+ T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients. Single-cell RNA and TCR sequencing of VZV-specific T cells shows that T cell activation pathways are significantly decreased after stimulation with VZV peptides in convalescent HZ patients. TCR clustering indicates that TCRs from HZ patients co-cluster more often together than TCRs from controls. Collectively, our results suggest that not only lower VZV-specific TCR diversity but also reduced functional TCR affinity for VZV-specific proteins in HZ patients leads to lower T cell activation and consequently affects the susceptibility for viral reactivation.
