Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cell Reports, Vol 43, Iss 4, Pp 114062- (2024)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2024.114062
Popis: 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.
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