학술논문
Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation
Document Type
article
Author
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
Source
Cell Reports, Vol 43, Iss 4, Pp 114062- (2024)
Subject
Language
English
ISSN
2211-1247
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.