ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Sensor Function for Butyrophilin 3A1 in Prenyl Pyrophosphate Stimulation of Human Vγ2Vδ2 T Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 73 citations in OpenAlex.
- A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing.Nature communications · 2023Article
- Article
- Mutations to the BTN2A1 Linker Region Impact Its Homodimerization and Its Cytoplasmic Interaction with Phospho-Antigen-Bound BTN3A1.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- BTN3A1 promotes tumor progression and radiation resistance in esophageal squamous cell carcinoma by regulating ULK1-mediated autophagy.Cell death & disease · 2022Article
- Generation of effector Vγ9Vδ2 T cells and evaluation of their response to phosphoantigen-loaded cells.STAR protocols · 2022Article
- Ligand-induced interactions between butyrophilin 2A1 and 3A1 internal domains in the HMBPP receptor complex.Cell chemical biology · 2022Article
- Prodrugs of pyrophosphates and bisphosphonates: disguising phosphorus oxyanions.RSC medicinal chemistry · 2022Review
- Potentiating Vγ9Vδ2 T cell proliferation and assessing their cytotoxicity towards adherent cancer cells at the single cell level.Biology open · 2022Article
- Comprehensive analyses of a tumor-infiltrating lymphocytes-related gene signature regarding the prognosis and immunologic features for immunotherapy in bladder cancer on the basis of WGCNA.Frontiers in immunology · 2022Article
- Our evolving understanding of the role of the γδ T cell receptor in γδ T cell mediated immunity.Biochemical Society transactions · 2021Review
- Listeria monocytogenes-infected human monocytic derived dendritic cells activate Vγ9Vδ2 T cells independently of HMBPP production.Scientific reports · 2021Article
- Prognostic and Therapeutic Significance of BTN3A Proteins in Tumors.Journal of Cancer · 2021Review
- PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer.Oncoimmunology · 2021Article
- Aryloxy Diester Phosphonamidate Prodrugs of Phosphoantigens (ProPAgens) as Potent Activators of Vγ9/Vδ2 T-Cell Immune Responses.Journal of medicinal chemistry · 2020Article
- Ligand recognition by the γδ TCR and discrimination between homeostasis and stress conditions.Cellular & molecular immunology · 2020Review
- Activation of Human Vδ2Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Review
- The Dual Roles of Human γδ T Cells: Anti-Tumor or Tumor-Promoting.Frontiers in immunology · 2020Review
- Granulysin: killer lymphocyte safeguard against microbes.Current opinion in immunology · 2019Review
- Synthesis and Bioactivity of the Alanyl Phosphonamidate Stereoisomers Derived from a Butyrophilin Ligand.ACS medicinal chemistry letters · 2019Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Vγ2Vδ2 T cells play important roles in human immunity to pathogens and in cancer immunotherapy by responding to isoprenoid metabolites, such as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate and isopentenyl pyrophosphate. The Ig superfamily protein butyrophilin (BTN)3A1 was shown to be required for prenyl pyrophosphate stimulation. We proposed that the intracellular B30.2 domain of BTN3A1 binds prenyl pyrophosphates, resulting in a change in the extracellular BTN3A1 dimer that is detected by Vγ2Vδ2 TCRs. Such B30.2 binding was demonstrated recently. However, other investigators reported that the extracellular BTN3A1 IgV domain binds prenyl pyrophosphates, leading to the proposal that the Vγ2Vδ2 TCR recognizes the complex. To distinguish between these mechanisms, we mutagenized residues in the two binding sites and tested the mutant BTN3A1 proteins for their ability to mediate prenyl pyrophosphate stimulation of Vγ2Vδ2 T cells to proliferate and secrete TNF-α. Mutagenesis of residues in the IgV site had no effect on Vγ2Vδ2 T cell proliferation or secretion of TNF-α. In contrast, mutagenesis of residues within the basic pocket and surrounding V regions of the B30.2 domain abrogated prenyl pyrophosphate-induced proliferation. Mutations of residues making hydrogen bonds to the pyrophosphate moiety also abrogated TNF-α secretion, as did mutation of aromatic residues making contact with the alkenyl chain. Some mutations further from the B30.2 binding site also diminished stimulation, suggesting that the B30.2 domain may interact with a second protein. These findings support intracellular sensing of prenyl pyrophosphates by BTN3A1 rather than extracellular presentation.
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