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Title: | Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation | Authors: | Boeren, Marlies de Vrij, Nicky Ha, My K. Valkiers, Sebastiaan Souquette, Aisha Gielis , Sofie Kuznetsova, Maria Schippers, Jolien Bartholomeus, Esther Van den Bergh , Johan Michels, Nele Aerts, Olivier Leysen, Julie Bervoets, An Lambert, Julien Leuridan, Elke Wens, Johan Peeters, Karin Emonds, Marie-Paule Elias, George Vandamme, Niels Jansens, Hilde Adriaensen, Wim Suls, Arvid Vanhee, Stijn HENS, Niel Smits, Evelien Van Damme, Pierre Thomas, Paul G. Beutels, Philippe Ponsaerts , Peter Van Tendeloo, Viggo Delputte, Peter Laukens, Kris Meysman, Pieter OGUNJIMI, Benson |
Issue Date: | 2024 | Publisher: | CELL PRESS | Source: | Cell Reports, 43 (4) , p. 1 -19 | 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. | Notes: | Ogunjimi, B (corresponding author), Univ Antwerp, Vaccine & Infect Dis Inst, Antwerp Ctr Translat Immunol & Virol ACTIV, Antwerp, Belgium.; Ogunjimi, B (corresponding author), Antwerp Unit Data Anal & Computat Immunol & Sequen, Antwerp, Belgium.; Ogunjimi, B (corresponding author), Univ Antwerp, Vaccine & Infect Dis Inst, Ctr Hlth Econ Res & Modelling Infect Dis CHERMID, Antwerp, Belgium.; Bervoets, A (corresponding author), Antwerp Univ Hosp, Dept Dermatol, Antwerp, Belgium.; Ogunjimi, B (corresponding author), Antwerp Univ Hosp, Dept Paediat, Antwerp, Belgium. benson.ogunjimi@uantwerp.be |
Keywords: | CP: Immunology;T cell receptor;TCR;VZV;shingles;varicella-zoster;Humans;Female;Middle Aged;Male;CD4-Positive T-Lymphocytes;Aged;Adult;Epitopes, T-Lymphocyte;Herpes Zoster;Receptors, Antigen, T-Cell;Lymphocyte Activation;Herpesvirus 3, Human | Document URI: | http://hdl.handle.net/1942/43104 | ISSN: | 2211-1247 | e-ISSN: | 2211-1247 | DOI: | 10.1016/j.celrep.2024.114062 | ISI #: | 001223579800001 | Rights: | 2024 The Authors. Published by Elsevier Inc. 1 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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