|
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)
|
|
|
|
| |
|