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

M Boeren; N de Vrij; MK Ha; S Valkiers; A Souquette; S Gielis; M Kuznetsova; J Schippers; E Bartholomeus; J van den Bergh; N Michels; O Aerts; J Leysen; A Bervoets; J Lambert; E Leuridan; J Wens; K Peeters; MP Emonds; G Elias; N Vandamme; H Jansens; W Adriaensen; A Suls; S Vanhee; N Hens; E Smits; P Van Damme; PG Thomas; P Beutels; P Ponsaerts; V Van Tendeloo; P Delputte; K Laukens; P Meysman; B Ogunjimi

doi:10.1016/j.celrep.2024.114062

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

M Boeren, N de Vrij, MK Ha, S Valkiers, A Souquette, S Gielis, M Kuznetsova, J Schippers, E Bartholomeus, J van den Bergh, N Michels, O Aerts, J Leysen, A Bervoets, J Lambert, E Leuridan, J Wens, K Peeters, MP Emonds, G EliasN Vandamme, H Jansens, W Adriaensen, A Suls, S Vanhee, N Hens, E Smits, P Van Damme, PG Thomas, P Beutels, P Ponsaerts, V Van Tendeloo, P Delputte, K Laukens, P Meysman, B Ogunjimi

Research output: Contribution to journal › A1: Web of Science-article › peer-review

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.

Original language	English
Journal	Cell Reports
Volume	43
Issue number	4
Pages (from-to)	1-19
Number of pages	19
ISSN	2211-1247
DOIs	https://doi.org/10.1016/j.celrep.2024.114062
Publication status	Published - 2024

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Boeren, M., de Vrij, N., Ha, MK., Valkiers, S., Souquette, A., Gielis, S., Kuznetsova, M., Schippers, J., Bartholomeus, E., van den Bergh, J., Michels, N., Aerts, O., Leysen, J., Bervoets, A., Lambert, J., Leuridan, E., Wens, J., Peeters, K., Emonds, MP., ... Ogunjimi, B. (2024). Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation. Cell Reports, 43(4), 1-19. https://doi.org/10.1016/j.celrep.2024.114062

@article{e734d6ff774b4ebc8a3836fb88274ca1,

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

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.",

author = "M Boeren and {de Vrij}, N and MK Ha and S Valkiers and A Souquette and S Gielis and M Kuznetsova and J Schippers and E Bartholomeus and {van den Bergh}, J and N Michels and O Aerts and J Leysen and A Bervoets and J Lambert and E Leuridan and J Wens and K Peeters and MP Emonds and G Elias and N Vandamme and H Jansens and W Adriaensen and A Suls and S Vanhee and N Hens and E Smits and {Van Damme}, P and PG Thomas and P Beutels and P Ponsaerts and {Van Tendeloo}, V and P Delputte and K Laukens and P Meysman and B Ogunjimi",

note = "FTX;DOAJ;CC BY",

year = "2024",

doi = "10.1016/j.celrep.2024.114062",

language = "English",

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pages = "1--19",

journal = "Cell Reports",

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Boeren, M, de Vrij, N, Ha, MK, Valkiers, S, Souquette, A, Gielis, S, Kuznetsova, M, Schippers, J, Bartholomeus, E, van den Bergh, J, Michels, N, Aerts, O, Leysen, J, Bervoets, A, Lambert, J, Leuridan, E, Wens, J, Peeters, K, Emonds, MP, Elias, G, Vandamme, N, Jansens, H, Adriaensen, W, Suls, A, Vanhee, S, Hens, N, Smits, E, Van Damme, P, Thomas, PG, Beutels, P, Ponsaerts, P, Van Tendeloo, V, Delputte, P, Laukens, K, Meysman, P & Ogunjimi, B 2024, 'Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation', Cell Reports, vol. 43, no. 4, pp. 1-19. https://doi.org/10.1016/j.celrep.2024.114062

TY - JOUR

T1 - Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation

AU - Boeren, M

AU - de Vrij, N

AU - Ha, MK

AU - Valkiers, S

AU - Souquette, A

AU - Gielis, S

AU - Kuznetsova, M

AU - Schippers, J

AU - Bartholomeus, E

AU - van den Bergh, J

AU - Michels, N

AU - Aerts, O

AU - Leysen, J

AU - Bervoets, A

AU - Lambert, J

AU - Leuridan, E

AU - Wens, J

AU - Peeters, K

AU - Emonds, MP

AU - Elias, G

AU - Vandamme, N

AU - Jansens, H

AU - Adriaensen, W

AU - Suls, A

AU - Vanhee, S

AU - Hens, N

AU - Smits, E

AU - Van Damme, P

AU - Thomas, PG

AU - Beutels, P

AU - Ponsaerts, P

AU - Van Tendeloo, V

AU - Delputte, P

AU - Laukens, K

AU - Meysman, P

AU - Ogunjimi, B

N1 - FTX;DOAJ;CC BY

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=itm_wosliteitg&SrcAuth=WosAPI&KeyUT=WOS:001223579800001&DestLinkType=FullRecord&DestApp=WOS_CPL

U2 - 10.1016/j.celrep.2024.114062

DO - 10.1016/j.celrep.2024.114062

M3 - A1: Web of Science-article

C2 - 38588339

SN - 2211-1247

VL - 43

SP - 1

EP - 19

JO - Cell Reports

JF - Cell Reports

IS - 4

ER -

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

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