Title
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Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation
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Author
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Abstract
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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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Language
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English
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Source (journal)
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Cell reports
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Publication
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2024
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ISSN
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2211-1247
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DOI
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10.1016/J.CELREP.2024.114062
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Volume/pages
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43
:4
(2024)
, p. 1-18
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Article Reference
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114062
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ISI
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001223579800001
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Pubmed ID
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38588339
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Full text (Publisher's DOI)
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Full text (open access)
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