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A Brief Molecular History of Vγ9Vδ2 TCR-Mediated Phosphoantigen Sensing.
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Department of Immunology and Immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK.
Vγ9Vδ2 T-cells are universally present in humans and represent one of the most prevalent TCR reactivities, evolutionarily conserved across diverse mammalian species. They are an innate-like subset featuring a semi-invariant TCR repertoire that drives their well-recognized reactivity to small, non-peptidic phosphoantigens (pAg). Crucially, they can distinguish between highly immunostimulatory microbially derived pAg and much less potent host-derived pAg, with the former effectively acting as a pathogen associated molecular pattern (PAMP) and the Vγ9Vδ2 TCR as a surrogate pattern recognition receptor (PRR).
View Article and Find Full Text PDFIron overload in HFE-related hemochromatosis severely impairs Vδ2+ γδ T-cell homeostasis.
Blood
July 2025
Department of Pediatric Hematology and Oncology, University Children's Hospital Tuebingen, Tübingen, Germany.
HFE-related hemochromatosis induces systemic iron overload. Although extensive studies indicate a pivotal role for iron homeostasis in αβ T-cell immunity, its effect on γδ T cells is unknown. Here, we found a reversal of the Vδ2+/Vδ2- ratio in the γδ T-cell compartment as a feature of hemochromatosis, which is associated with a Vδ2+ population that cannot be enriched by zoledronic acid (ZOL) stimulation, despite evidence of T-cell receptor (TCR)-ligand formation and strong proliferative behavior.
View Article and Find Full Text PDFInvestigation of structural and dynamic properties of the Butyrophilin BTN3A1/BTN2A1 cytoplasmic complex by F solution NMR.
FASEB J
March 2025
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, USA.
Butyrophilin 3A1 (BTN3A1) is an integral membrane protein capable of detecting phosphoantigens, like (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP), through its internal B30.2 domain. Detection of phosphoantigens leads to interactions with butyrophilin 2A1 and the subsequent activation of γδ-T cells.
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December 2024
Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.
Epstein-Barr virus is highly associated with nasopharyngeal carcinoma (NPC) with genes expressed for tumor transformation or maintenance of viral latency, but there are certain genes that can modulate immune molecules. Butyrophilin 2A1 (BTN2A1) is an important activating protein for presenting phosphoantigens for recognition by Vγ9Vδ2 T cells to achieve antitumor activities. We have previously shown that Vγ9Vδ2 T cells achieve efficacy against NPC when BTN2A1 and BTN3A1 are upregulated by stimulating EBV gene expression, particularly LMP1.
View Article and Find Full Text PDFInvestigating potential drug targets for IgA nephropathy and membranous nephropathy through multi-queue plasma protein analysis: a Mendelian randomization study based on SMR and co-localization analysis.
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November 2024
Department of Clinical Laboratory, Jinhua Maternal and Child Health Care Hospital, Jinhua, Zhejiang, 321000, China.
Article Synopsis
- Membranous nephropathy (MN) and IgA nephropathy (IgAN) are difficult to treat, with current therapies mainly relieving symptoms but often failing to improve outcomes, highlighting the need for new drug targets.
- Researchers used large genome-wide association study (GWAS) data to establish connections between specific plasma proteins and these kidney diseases, employing various analytical methods to confirm the significance of their findings.
- The study identified four proteins linked to MN and three to IgAN, suggesting potential new targets for treatment; key proteins like PLA2R1 and NFKB1 showed strong associations with MN risk, while others like AIF1 offered protective effects against IgAN.