Publication
Title
Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation
Author
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.
Language
English
Source (journal)
Cell reports
Publication
2024
ISSN
2211-1247
DOI
10.1016/J.CELREP.2024.114062
Volume/pages
43 :4 (2024) , p. 1-18
Article Reference
114062
ISI
001223579800001
Pubmed ID
38588339
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
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Record
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Creation 11.04.2024
Last edited 28.05.2024
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