Evidence map›Paper›PMID 25637025›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2015

Activation of human γδ T cells by cytosolic interactions of BTN3A1 with soluble phosphoantigens and the cytoskeletal adaptor periplakin.

David A Rhodes, Hung-Chang Chen, Amanda J Price, Anthony H Keeble, Martin S Davey, Leo C James, Matthias Eberl, John Trowsdale

Open access · hybridAbstract read
In one paragraph

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 100 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed, 1 pooled it
7.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

100 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  5. Article
  6. International journal of molecular sciences · 2025
    Article
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  10. Review
  11. Investigation of structural and dynamic properties of the Butyrophilin BTN3A1/BTN2A1 cytoplasmic complex byFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  12. Article
  13. The Evolving Portrait of γδ TCR Recognition Determinants.Journal of immunology (Baltimore, Md. : 1950) · 2024
    Review
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  15. Article
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40 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 4 countries.

David A RhodesImmunology Division, Department of Pathology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 0XY, United Kingdom; dar32@cam.ac.uk.
Hung-Chang ChenCardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom; and.
Amanda J PriceProtein and Nucleic Acid Chemistry Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
Anthony H KeebleProtein and Nucleic Acid Chemistry Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
Martin S DaveyCardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom; and.
Leo C JamesProtein and Nucleic Acid Chemistry Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
Matthias EberlCardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom; and.
John TrowsdaleImmunology Division, Department of Pathology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 0XY, United Kingdom;
Cardiff University · GBMedical Research Council · GBCambridge School · PTInstitute for Medical Research · MYMRC Laboratory of Molecular Biology · GB

Funding

Medical Research Council G0901682Medical Research Council MC_U105181010Wellcome Trust 089821Wellcome Trust 100140
6 · The paper itself

Abstract

The three butyrophilin BTN3A molecules, BTN3A1, BTN3A2, and BTN3A3, are members of the B7/butyrophilin-like group of Ig superfamily receptors, which modulate the function of T cells. BTN3A1 controls activation of human Vγ9/Vδ2 T cells by direct or indirect presentation of self and nonself phosphoantigens (pAg). We show that the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate binds to the intracellular B30.2 domain of BTN3A1 with an affinity of 1.1 μM, whereas the endogenous pAg isopentenyl pyrophosphate binds with an affinity of 627 μM. Coculture experiments using knockdown cell lines showed that in addition to BTN3A1, BTN3A2 and BTN3A3 transmit activation signals to human γδ T cells in response to (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate and the aminobisphosphonate drug zoledronate that causes intracellular accumulation of isopentenyl pyrophosphate. The plakin family member periplakin, identified in yeast two-hybrid assays, interacted with a membrane-proximal di-leucine motif, located proximal to the B30.2 domain in the BTN3A1 cytoplasmic tail. Periplakin did not interact with BTN3A2 or BTN3A3, which do not contain the di-leucine motif. Re-expression into a BTN3A1 knockdown line of wild-type BTN3A1, but not of a variant lacking the periplakin binding motif, BTN3A1Δexon5, restored γδ T cell responses, demonstrating a functional role for periplakin interaction. These data, together with the widespread expression in epithelial cells, tumor tissues, and macrophages detected using BTN3A antiserum, are consistent with complex functions for BTN3A molecules in tissue immune surveillance and infection, linking the cell cytoskeleton to γδ T cell activation by indirectly presenting pAg to the Vγ9/Vδ2 TCR.

Indexed as

AnimalsAntigensAntigens, CDBinding SitesButyrophilinsCell Line, TumorChlorocebus aethiopsCOS CellsCrystallography, X-RayDiphosphatesDiphosphonatesEscherichia coliGene Expression RegulationHemiterpenesHumansImidazoles4-hydroxy-3-methylbut-2-enyl pyrophosphateAntigensAntigens, CDBTN3A1 protein, humanBTN3A2 protein, humanButyrophilinsDiphosphatesDiphosphonatesHemiterpenesImidazolesisopentenyl pyrophosphateMembrane ProteinsOrganophosphorus CompoundsPhosphoproteinsPlakinsPPL protein, humanReceptors, Antigen, T-Cell, gamma-deltaRecombinant Fusion ProteinsZoledronic Acid

Identifiers

PMID25637025
PMCPMC4337483
OpenAlexW2136199333

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

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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.