Evidence map›Paper›PMID 36824912›Full record

ArticleResearch square2023

Division of labor and cooperation between different butyrophilin proteins controls phosphoantigen-mediated activation of human γδ T cells.

Mohindar Murugesh Karunakaran, Hariharan Subramanian, Yiming Jin, Fiyaz Mohammed, Brigitte Kimmel, Claudia Juraske, Lisa Starick, Anna Nöhren, Nora Länder, Carrie R Willcox and 7 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 3 countries.

Mohindar Murugesh KarunakaranInstitute for Virology und Immunobiology, University of Würzburg, Würzburg, Germany.
Hariharan SubramanianInstitute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany.
Yiming JinDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA; Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA.
Fiyaz MohammedInstitute of Immunology and Immunotherapy, University of Birmingham, UK.
Brigitte KimmelUniversity Hospital Wuerzburg, Department of Internal Medicine II and Comprehensive Cancer Center (CCC) Mainfranken Wuerzburg, Wuerzburg Germany.
Claudia JuraskeSignaling Research Centers BIOSS and CIBSS and Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany; Centre for Chronic Immunodeficiency (CCI), Faculty of Medicine, University of Freiburg; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany.
Lisa StarickInstitute for Virology und Immunobiology, University of Würzburg, Würzburg, Germany.
Anna NöhrenInstitute for Virology und Immunobiology, University of Würzburg, Würzburg, Germany.
Nora LänderInstitute for Virology und Immunobiology, University of Würzburg, Würzburg, Germany.
Carrie R WillcoxInstitute of Immunology and Immunotherapy, University of Birmingham, UK.
Rohit SinghDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA; Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA.
Wolfgang W SchamelSignaling Research Centers BIOSS and CIBSS and Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany; Centre for Chronic Immunodeficiency (CCI), Faculty of Medicine, University of Freiburg; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany.
Viacheslav O NikolaevInstitute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany.
Volker KunzmannUniversity Hospital Wuerzburg, Department of Internal Medicine II and Comprehensive Cancer Center (CCC) Mainfranken Wuerzburg, Wuerzburg Germany.
Andrew J WiemerDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA; Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA.
Benjamin E Willcox6Institute of Immunology and Immunotherapy, University of Birmingham, UK.
Thomas HerrmannInstitute for Virology und Immunobiology, University of Würzburg, Würzburg, Germany.
University of Würzburg · DEUniversity of Birmingham · GBUniversity of Connecticut · USComprehensive Cancer Center Mainfranken · DEUniversität Hamburg · DEUniversity of Freiburg · DE

Funding

Role of immune modulating butyrophilins in gamma delta T cell activationR01AI150869 · NIAID · UNIVERSITY OF CONNECTICUT STORRS · PI VINOGRADOVA, OLGA, WIEMER, ANDREW J · 2020 to 2024
$2.0M
Synthesis and evaluation of BTN3A1 ligands for cancer immunotherapyR01CA266138 · NCI · UNIVERSITY OF CONNECTICUT STORRS · PI ANDREW J WIEMER · 2022 to 2026
$1.8M
NCI NIH HHS R01 CA266138NIAID NIH HHS R01 AI150869Wellcome Trust
6 · The paper itself

Abstract

Butyrophilin (BTN)-3A and BTN2A1 molecules control TCR-mediated activation of human Vγ9Vδ2 T-cells triggered by phosphoantigens (PAg) from microbes and tumors, but the molecular rules governing antigen sensing are unknown. Here we establish three mechanistic principles of PAg-action. Firstly, in humans, following PAg binding to the BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the V-domain of BTN3A2/BTN3A3. Moreover, PAg/B30.2 interaction, and the critical γδ-T-cell-activating V-domain, localize to different molecules. Secondly, this distinct topology as well as intracellular trafficking and conformation of BTN3A heteromers or ancestral-like BTN3A homomers are controlled by molecular interactions of the BTN3 juxtamembrane region. 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 division of labor in BTN proteins deepens understanding of PAg sensing and elucidates a mode of action potentially applicable to other BTN/BTNL family members.

Indexed as

BTN2A1BTN3A1ButyrophilinjuxtamembranephosphoantigensTCRVγ9Vδ2 T cellsγδ T cells

Identifiers

PMID36824912
PMCPMC9949253
OpenAlexW4320892973

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.