Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation.
Cell Rep
; 43(4): 114062, 2024 Apr 23.
Article
en En
| MEDLINE
| ID: mdl-38588339
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
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Receptores de Antígenos de Linfocitos T
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Herpesvirus Humano 3
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Herpes Zóster
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cell Rep
Año:
2024
Tipo del documento:
Article