ArticleNature communications2023
A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Insights into the Mechanism of Action of Phosphoantigen Prodrugs on Vγ9Vδ2 T Cell Activation.ACS pharmacology & translational science · 2026Article
- γδ T cells in colorectal and liver cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Phosphoantigen-driven dissociation of butyrophilin oligomers activates γδ T cells.Cell discovery · 2026Article
- NanoBRET Saturation Analysis with a Novel HaloTag Ligand Reveals Butyrophilin Heteromeric Interactions Controlling γ9δ2 T Cell Activation.ACS chemical biology · 2026Article
- Benzoic Acid Derivatives Improve Plasma Stability of Diester Butyrophilin Ligand Prodrugs.Journal of medicinal chemistry · 2026Article
- Cell stress activates γ9δ2 T cells via endogenous phosphoantigens and butyrophilin complex dynamics.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Metabolic control of innate-like T cells.Nature reviews. Immunology · 2026Review
- Vγ9Vδ2 T cells in tuberculosis: protective immunity and translational perspectives.Frontiers in immunology · 2026Review
- Review
- Cis- and trans-binding chimeric costimulatory receptors enhance T-cell fitness and tumor control.Cellular & molecular immunology · 2026Article
- Targeted proteomics reveals immune protein patterns in serum from patients with calcific aortic stenosis.iScience · 2025Article
- Gut microbial metabolites in cancer immunomodulation.Molecular cancer · 2025Review
- γ9δ2 T cells detect mevalonate diphosphate via BTN3A3.Cellular and molecular life sciences : CMLS · 2025Article
- Article
- Disrupting the balance between activating and inhibitory receptors of γδT cells for effective cancer immunotherapy.Nature reviews. Cancer · 2025Review
- Iron overload in HFE-related hemochromatosis severely impairs Vδ2+ γδ T-cell homeostasis.Blood · 2025Article
- Article
- Mechanisms and Functions of γδ T Cells in Tumor Cell Recognition.Current oncology (Toronto, Ont.) · 2025Review
- A Brief Molecular History of Vγ9Vδ2 TCR-Mediated Phosphoantigen Sensing.Immunological reviews · 2025Review
- Mapping the extracellular molecular architecture of the pAg-signaling complex with α-Butyrophilin antibodies.Scientific reports · 2025Article
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Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
Abstract
Butyrophilin (BTN)-3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg sensing remain largely unknown. Here, we establish three mechanistic principles of PAg-mediated γδ T cell activation. First, in humans, following PAg binding to the intracellular BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the extracellular V-domain of BTN3A2/BTN3A3. Moreover, the localization of both protein domains on different chains of the BTN3A homo-or heteromers is essential for efficient PAg-mediated activation. Second, the formation of BTN3A homo-or heteromers, which differ in intracellular trafficking and conformation, is controlled by molecular interactions between the juxtamembrane regions of the BTN3A chains. Finally, the ability of PAg not simply to bind BTN3A-B30.2, but to promote its subsequent interaction with the BTN2A1-B30.2 domain, is essential for T-cell activation. Defining these determinants of cooperation and the division of labor in BTN proteins improves our understanding of PAg sensing and elucidates a mode of action that may apply to other BTN family members.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.