Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation
- Author
- Marlies Boeren, Nicky de Vrij, My K. Ha, Sebastiaan Valkiers, Aisha Souquette, Sofie Gielis, Maria Kuznetsova, Jolien Schippers, Esther Bartholomeus, Johan Van den Bergh, Nele Michels, Olivier Aerts, Julie Leysen, An Bervoets, Julien Lambert, Elke Leuridan, Johan Wens, Karin Peeters, Marie-Paule Emonds, George Elias, Niels Vandamme (UGent) , Hilde Jansens, Wim Adriaensen, Arvid Suls, Stijn Vanhee (UGent) , Niel Hens, Evelien Smits, Pierre Van Damme, Paul G. Thomas, Philippe Beutels, Peter Ponsaerts, Viggo Van Tendeloo, Peter Delputte, Kris Laukens, Pieter Meysman and Benson Ogunjimi (UGent)
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- 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.
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HYJN4BMX952Z6Z3PN3HGEC7W
- MLA
- Boeren, Marlies, et al. “Lack of Functional TCR-Epitope Interaction Is Associated with Herpes Zoster through Reduced Downstream T Cell Activation.” CELL REPORTS, vol. 43, no. 4, 2024, pp. 1–19, doi:10.1016/j.celrep.2024.114062.
- APA
- Boeren, M., de Vrij, N., Ha, M. K., Valkiers, S., Souquette, A., Gielis, S., … 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
- Chicago author-date
- Boeren, Marlies, Nicky de Vrij, My K. Ha, Sebastiaan Valkiers, Aisha Souquette, Sofie Gielis, Maria Kuznetsova, et al. 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.
- Chicago author-date (all authors)
- Boeren, Marlies, Nicky de Vrij, My K. Ha, Sebastiaan Valkiers, Aisha Souquette, Sofie Gielis, Maria Kuznetsova, Jolien Schippers, Esther Bartholomeus, Johan Van den Bergh, Nele Michels, Olivier Aerts, Julie Leysen, An Bervoets, Julien Lambert, Elke Leuridan, Johan Wens, Karin Peeters, Marie-Paule Emonds, George Elias, Niels Vandamme, Hilde Jansens, Wim Adriaensen, Arvid Suls, Stijn Vanhee, Niel Hens, Evelien Smits, Pierre Van Damme, Paul G. Thomas, Philippe Beutels, Peter Ponsaerts, Viggo Van Tendeloo, Peter Delputte, Kris Laukens, Pieter Meysman, and Benson Ogunjimi. 2024. “Lack of Functional TCR-Epitope Interaction Is Associated with Herpes Zoster through Reduced Downstream T Cell Activation.” CELL REPORTS 43 (4): 1–19. doi:10.1016/j.celrep.2024.114062.
- Vancouver
- 1.Boeren M, de Vrij N, Ha MK, Valkiers S, Souquette A, Gielis S, et al. Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation. CELL REPORTS. 2024;43(4):1–19.
- IEEE
- [1]M. Boeren et al., “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, 2024.
@article{01HYJN4BMX952Z6Z3PN3HGEC7W,
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.}},
articleno = {{114062}},
author = {{Boeren, Marlies and de Vrij, Nicky and Ha, My K. and Valkiers, Sebastiaan and Souquette, Aisha and Gielis, Sofie and Kuznetsova, Maria and Schippers, Jolien and Bartholomeus, Esther and Van den Bergh, Johan and Michels, Nele and Aerts, Olivier and Leysen, Julie and Bervoets, An and Lambert, Julien and Leuridan, Elke and Wens, Johan and Peeters, Karin and Emonds, Marie-Paule and Elias, George and Vandamme, Niels and Jansens, Hilde and Adriaensen, Wim and Suls, Arvid and Vanhee, Stijn and Hens, Niel and Smits, Evelien and Van Damme, Pierre and Thomas, Paul G. and Beutels, Philippe and Ponsaerts, Peter and Van Tendeloo, Viggo and Delputte, Peter and Laukens, Kris and Meysman, Pieter and Ogunjimi, Benson}},
issn = {{2639-1856}},
journal = {{CELL REPORTS}},
language = {{eng}},
number = {{4}},
pages = {{114062:1--114062:19}},
title = {{Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation}},
url = {{http://doi.org/10.1016/j.celrep.2024.114062}},
volume = {{43}},
year = {{2024}},
}
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