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

Cell Rep. 2024 Apr 7;43(4):114062. doi: 10.1016/j.celrep.2024.114062. Online ahead of print.ABSTRACTThe 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.PMID:38588339 | DOI:10.1016/j.celrep.2024.114062
Source: Herpes - Category: Infectious Diseases Authors: Source Type: research