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Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell
Marlies Boeren1, Nicky de Vrij2, My K Ha3
1Laboratory 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.
Abstract:
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.
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