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Butyrophilin

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https://www.readbyqxmd.com/read/28461569/the-juxtamembrane-domain-of-butyrophilin-btn3a1-controls-phosphoantigen-mediated-activation-of-human-v%C3%AE-9v%C3%AE-2-t-cells
#1
Cassie-Marie Peigné, Alexandra Léger, Marie-Claude Gesnel, Fabienne Konczak, Daniel Olive, Marc Bonneville, Richard Breathnach, Emmanuel Scotet
Vγ9Vδ2 T lymphocytes are the major human peripheral γδ T cell subset, with broad reactivity against stressed human cells, including tumor cells. Vγ9Vδ2 T cells are specifically activated by small phosphorylated metabolites called phosphoantigens (PAg). Stress-induced changes in target cell PAg levels are specifically detected by butyrophilin (BTN)3A1, using its intracellular B30.2 domain. This leads to the activation of Vγ9Vδ2 T cells. In this study, we show that changes in the juxtamembrane domain of BTN3A1, but not its transmembrane domain, induce a markedly enhanced or reduced γδ T cell reactivity...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28405500/zoledronate-can-induce-colorectal-cancer-microenvironment-expressing-btn3a1-to-stimulate-effector-%C3%AE-%C3%AE-t-cells-with-antitumor-activity
#2
Maria Raffaella Zocchi, Delfina Costa, Roberta Venè, Francesca Tosetti, Nicoletta Ferrari, Simona Minghelli, Roberto Benelli, Stefano Scabini, Emanuele Romairone, Silvia Catellani, Aldo Profumo, Alessandro Poggi
Amino-bis-phosphonates (N-BPs) such as zoledronate (Zol) have been used in anticancer clinical trials due to their ability to upregulate pyrophosphate accumulation promoting antitumor Vγ9Vδ2 T cells. The butyrophilin 3A (BTN3A, CD277) family, mainly the BTN3A1 isoform, has emerged as an important structure contributing to Vγ9Vδ2 T cells stimulation. It has been demonstrated that the B30.2 domain of BTN3A1 can bind phosphoantigens (PAg) and drive the activation of Vγ9Vδ2 T cells through conformational changes of the extracellular domains...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28386905/butyrophilin-3a-btn3a-cd277-specific-antibody-20-1-differentially-activates-v%C3%AE-9v%C3%AE-2-tcr-clonotypes-and-interferes-with-phosphoantigen-activation
#3
Lisa Starick, Felipe Riano, Mohindar M Karunakaran, Volker Kunzmann, Jianqiang Li, Matthias Kreiss, Sabine Amslinger, Emmanuel Scotet, Daniel Olive, Gennaro De Libero, Thomas Herrmann
Phosphoantigens (PAg) like HMBPP ((E)-4-hydroxy-3-methyl-but-2-enyl diphosphate) and butyrophilin 3 (BTN3A, CD277)-specific monoclonal antibody (mAb) 20.1 induce TCR-mediated activation of Vγ9Vδ2 T cells. Here, we compared murine reporter cells transduced with Vγ9Vδ2 TCRs G115, D1C55 and MOP for the activation in culture with human RAJI cells and PAgs or mAb 20.1 and its single chain derivative (sc). All transductants responded readily to PAg but only TCR MOP γ-chain-expressing cells responded to mAb/sc 20...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28382515/evolutionary-and-polymorphism-analyses-reveal-the-central-role-of-btn3a2-in-the-concerted-evolution-of-the-btn3-gene-family
#4
Hassnae Afrache, Pierre Pontarotti, Laurent Abi-Rached, Daniel Olive
The butyrophilin 3 (BTN3) receptors are implicated in the T lymphocytes regulation and present a wide plasticity in mammals. In order to understand how these genes have been diversified, we studied their evolution and show that the three human BTN3 are the result of two successive duplications in Primates and that the three genes are present in Hominoids and the Old World Monkey groups. A thorough phylogenetic analysis reveals a concerted evolution of BTN3 characterized by a strong and recurrent homogenization of the region encoding the signal peptide and the immunoglobulin variable (IgV) domain in Hominoids, where the sequences of BTN3A1 or BTN3A3 are replaced by BTN3A2 sequence...
April 5, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28246015/exome-array-analysis-identifies-variants-in-spocd1-and-btn3a2-that-affect-risk-for-gastric-cancer
#5
Meng Zhu, Caiwang Yan, Chuanli Ren, Xiaodan Huang, Xun Zhu, Haiyong Gu, Meilin Wang, Shouyu Wang, Yong Gao, Yong Ji, Xiaoping Miao, Ming Yang, Jinfei Chen, Jiangbo Du, Tongtong Huang, Yue Jiang, Juncheng Dai, Hongxia Ma, Jianwei Zhou, Zhaoming Wang, Zhibin Hu, Guozhong Ji, Zhengdong Zhang, Hongbing Shen, Yongyong Shi, Guangfu Jin
BACKGROUND & AIMS: Several genetic variants have been associated with gastric cancer risk, although these account for only a fraction of gastric cancer cases. We aimed to identify low-frequency and other genetic variants that determine gastric cancer susceptibility. METHODS: We performed exome array analysis of DNA in blood samples from 1113 patients with gastric cancer, collected at hospitals from 2006 to 2010 in China, and 1848 individuals without cancer (controls) undergoing physical examinations...
February 25, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28218845/phosphinophosphonates-and-their-tris-pivaloyloxymethyl-prodrugs-reveal-a-negatively-cooperative-butyrophilin-activation-mechanism
#6
Rebekah R Shippy, Xiaochen Lin, Sherry S Agabiti, Jin Li, Brendan M Zangari, Benjamin J Foust, Michael M Poe, Chia-Hung Christine Hsiao, Olga Vinogradova, David F Wiemer, Andrew J Wiemer
Butyrophilin 3A1 (BTN3A1) binds small phosphorus-containing molecules, which initiates transmembrane signaling and activates butyrophilin-responsive cells. We synthesized several phosphinophosphonates and their corresponding tris-pivaloyloxymethyl (tris-POM) prodrugs and examined their effects on BTN3A1. An analog of (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) bound to BTN3A1 with intermediate affinity, which was enthalpy-driven. Docking studies revealed binding to the basic surface pocket and interactions between the allylic hydroxyl group and the BTN3A1 backbone...
March 1, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27957327/altered-expression-of-butyrophilin-btn-and-btn-like-btnl-genes-in-intestinal-inflammation-and-colon-cancer
#7
Cristina Lebrero-Fernández, Ulf Alexander Wenzel, Paulina Akeus, Ying Wang, Hans Strid, Magnus Simrén, Bengt Gustavsson, Lars G Börjesson, Susanna L Cardell, Lena Öhman, Marianne Quiding-Järbrink, Anna Bas-Forsberg
Several Butyrophilin (BTN) and Btn-like (BTNL) molecules control T lymphocyte responses, and are genetically associated with inflammatory disorders and cancer. In this study, we present a comprehensive expression analysis of human and murine BTN and BTNL genes in conditions associated with intestinal inflammation and cancer. Using real-time PCR, expression of human BTN and BTNL genes was analyzed in samples from patients with ulcerative colitis, irritable bowel syndrome, and colon tumors. Expression of murine Btn and Btnl genes was examined in mouse models of spontaneous colitis (Muc2(-/-)) and intestinal tumorigenesis (Apc(Min/+))...
June 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27914482/familial-vs-sporadic-sarcoidosis-btnl2-polymorphisms-clinical-presentations-and-outcomes-in-a-french-cohort
#8
Yves Pacheco, Alain Calender, Dominique Israël-Biet, Pascal Roy, Serge Lebecque, Vincent Cottin, Diane Bouvry, Hilario Nunes, Pascal Sève, Laurent Pérard, Gilles Devouassoux, Nathalie Freymond, Chahira Khouatra, Benoît Wallaert, Raphaelle Lamy, Mad-Hélénie Elsensohn, Claire Bardel, Dominique Valeyre
BACKGROUND: The occurrence of familial forms of sarcoidosis (OMIM 181100) suggests a genetic predisposition. The involvement of butyrophilin-like 2 (BTNL2) gene (rs2076530 variant) has to be investigated. RESULTS: The study performed independent analyses of BTNL2 polymorphism, clinical phenotypes, and outcomes in familial vs. sporadic presentations in 256 sporadic and 207 familial cases from 140 families. The logistic multivariate model showed that a young age at diagnosis and the combination of lung and skin involvement at diagnosis may distinguish sporadic from familial sarcoidosis (p = 0...
December 3, 2016: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/27911820/map4-regulated-dynein-dependent-trafficking-of-btn3a1-controls-the-tbk1-irf3-signaling-axis
#9
Minji Seo, Seong-Ok Lee, Ji-Hoon Kim, Yujin Hong, Seongchan Kim, Yeumin Kim, Dal-Hee Min, Young-Yun Kong, Jinwook Shin, Kwangseog Ahn
The innate immune system detects viral nucleic acids and induces type I interferon (IFN) responses. The RNA- and DNA-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor IFN-regulatory factor 3 (IRF3). Activation of the IFN signaling pathway is known to trigger the redistribution of key signaling molecules to punctate perinuclear structures, but the mediators of this spatiotemporal regulation have yet to be defined. Here we identify butyrophilin 3A1 (BTN3A1) as a positive regulator of nucleic acid-mediated type I IFN signaling...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27895170/prevention-of-v%C3%AE-9v%C3%AE-2-t-cell-activation-by-a-v%C3%AE-9v%C3%AE-2-tcr-nanobody
#10
Renée C G de Bruin, Anita G M Stam, Anna Vangone, Paul M P van Bergen En Henegouwen, Henk M W Verheul, Zsolt Sebestyén, Jürgen Kuball, Alexandre M J J Bonvin, Tanja D de Gruijl, Hans J van der Vliet
Vγ9Vδ2 T cell activation plays an important role in antitumor and antimicrobial immune responses. However, there are conditions in which Vγ9Vδ2 T cell activation can be considered inappropriate for the host. Patients treated with aminobisphosphonates for hypercalcemia or metastatic bone disease often present with a debilitating acute phase response as a result of Vγ9Vδ2 T cell activation. To date, no agents are available that can clinically inhibit Vγ9Vδ2 T cell activation. In this study, we describe the identification of a single domain Ab fragment directed to the TCR of Vγ9Vδ2 T cells with neutralizing properties...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27641500/epithelia-use-butyrophilin-like-molecules-to-shape-organ-specific-%C3%AE-%C3%AE-t-cell-compartments
#11
Rafael Di Marco Barros, Natalie A Roberts, Robin J Dart, Pierre Vantourout, Anett Jandke, Oliver Nussbaumer, Livija Deban, Sara Cipolat, Rosie Hart, Maria Luisa Iannitto, Adam Laing, Bradley Spencer-Dene, Philip East, Deena Gibbons, Peter M Irving, Pablo Pereira, Ulrich Steinhoff, Adrian Hayday
Many body surfaces harbor organ-specific γδ T cell compartments that contribute to tissue integrity. Thus, murine dendritic epidermal T cells (DETCs) uniquely expressing T cell receptor (TCR)-Vγ5 chains protect from cutaneous carcinogens. The DETC repertoire is shaped by Skint1, a butyrophilin-like (Btnl) gene expressed specifically by thymic epithelial cells and suprabasal keratinocytes. However, the generality of this mechanism has remained opaque, since neither Skint1 nor DETCs are evolutionarily conserved...
September 22, 2016: Cell
https://www.readbyqxmd.com/read/27628321/different-modes-of-variation-for-each-bg-lineage-suggest-different-functions
#12
John Chattaway, R Andrei Ramirez-Valdez, Paul E Chappell, Joseph J E Caesar, Susan M Lea, Jim Kaufman
Mammalian butyrophilins have various important functions, one for lipid binding but others as ligands for co-inhibition of αβ T cells or for stimulation of γδ T cells in the immune system. The chicken BG homologues are dimers, with extracellular immunoglobulin variable (V) domains joined by cysteines in the loop equivalent to complementarity-determining region 1 (CDR1). BG genes are found in three genomic locations: BG0 on chromosome 2, BG1 in the classical MHC (the BF-BL region) and many BG genes in the BG region just outside the MHC...
September 2016: Open Biology
https://www.readbyqxmd.com/read/27619996/butyrophilin-3a-cd277-dependent-activation-of-human-%C3%AE-%C3%AE-t-cells-accessory-cell-capacity-of-distinct-leukocyte-populations
#13
Patrik Theodor Nerdal, Christian Peters, Hans-Heinrich Oberg, Hristo Zlatev, Marcus Lettau, Elgar Susanne Quabius, Sofia Sousa, Daniel Gonnermann, Seppo Auriola, Daniel Olive, Jorma Määttä, Ottmar Janssen, Dieter Kabelitz
Human Vγ9Vδ2 T cells recognize in a butyrophilin 3A/CD277-dependent way microbial (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) or endogenous pyrophosphates (isopentenyl pyrophosphate [IPP]). Nitrogen-bisphosphonates such as zoledronic acid (ZOL) trigger selective γδ T cell activation because they stimulate IPP production in monocytes by inhibiting the mevalonate pathway downstream of IPP synthesis. We performed a comparative analysis of the capacity of purified monocytes, neutrophils, and CD4 T cells to serve as accessory cells for Vγ9Vδ2 T cell activation in response to three selective but mechanistically distinct stimuli (ZOL, HMBPP, agonistic anti-CD277 mAb)...
September 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27532663/analysis-of-the-expression-and-single-nucleotide-variant-frequencies-of-the-butyrophilin-like-2-gene-in-patients-with-uveal-melanoma
#14
Adriana Amaro, Federica Parodi, Konrad Diedrich, Giovanna Angelini, Cornelia Götz, Silvia Viaggi, Irena Maric, Domenico Coviello, Maria Pia Pistillo, Anna Morabito, Mario Mandalà, Paola Ghiorzo, Paola Visconti, Marina Gualco, Luca Anselmi, Roberto Puzone, Francesco Lanza, Carlo Mosci, Federica Raggi, Maria Carla Bosco, Luigi Varesio, Michael Zeschnigk, Laura Spano, Paola Queirolo, Ulrich Pfeffer
Importance: Chromosome 6p amplification is associated with more benign behavior for uveal melanomas (UMs) with an otherwise high risk of metastasis conferred by chromosome 3 monosomy. Chromosome 6p contains several members of the B7 family of immune regulator genes, including butyrophilin-like 2 (BTNL2; OMIM, 606000), which is associated with prostate cancer risk and autoimmune diseases. Objective: To investigate the expression and variant allele frequencies of BTNL2, a candidate gene for chromosome 6 amplification, in patients with UM...
October 1, 2016: JAMA Ophthalmology
https://www.readbyqxmd.com/read/27528202/the-ontogeny-of-butyrophilin-like-btnl-1-and-btnl6-in-murine-small-intestine
#15
Cristina Lebrero-Fernández, Anna Bas-Forsberg
Murine Butyrophilin-like (Btnl) 1 and Btnl6 are primarily restricted to intestinal epithelium where they regulate the function of intraepithelial T lymphocytes. We recently demonstrated that Btnl1 and Btnl6 can form an intra-family heterocomplex and that the Btnl1-Btnl6 complex selectively expands Vγ7Vδ4 TCR IELs. To define the regulation of Btnl expression in the small intestine during ontogeny we examined the presence of Btnl1 and Btnl6 in the small bowel of newborn to 4-week-old mice. Although RNA expression of Btnl1 and Btnl6 was detected in the small intestine at day 0, Btnl1 and Btnl6 protein expression was substantially delayed and was not detectable in the intestinal epithelium until the mice reached 2-3 weeks of age...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27491008/protective-immune-responses-of-major-v%C3%AE-2v%C3%AE-2-t-cell-subset-in-m-tuberculosis-infection
#16
Zheng W Chen
Recent observation that prenyl pyrophosphates bind the Ig superfamily protein butyrophilin 3A1 (BTN3A1) suggests that modifying BTN3A1 activates major γδ T-cell subset, Vγ2Vδ2 T cells. Studies also show that microbial phosphoantigen HMBPP is required for expansion, pulmonary response, effector functions and memory polarization of Vγ2Vδ2 T cells during infections. Broad repertoires of cytokines involve expansion, recall-like expansion and effector functions of Vγ2Vδ2 T cells after Mtb infection or vaccination...
August 1, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27472712/the-btnl2-g16071a-gene-polymorphism-increases-granulomatous-disease-susceptibility-a-meta-analysis-including-fprp-test-of-8710-participants
#17
Xiang Tong, Yao Ma, Xundong Niu, Zhipeng Yan, Sitong Liu, Bo Peng, Shifeng Peng, Hong Fan
OBJECTIVE: The butyrophilin-like 2 (BTNL2) G16071A gene polymorphism has been implicated in the susceptibility to granulomatous diseases, but the results were inconclusive. The objective of the current study was to precisely explore the relationship between BTNL2 G16071A gene polymorphism and granulomatous disease susceptibility by the meta-analysis including false-positive report probability (FPRP) test. METHODS: A systematic literature search in the PubMed, Embase, and Wanfang databases, China National Knowledge Internet, and commercial Internet search engines was conducted to identify studies published up to April 1, 2016...
July 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27357166/xanthine-oxidoreductase-mediates-membrane-docking-of-milk-fat-droplets-but-is-not-essential-for-apocrine-lipid-secretion
#18
Jenifer Monks, Monika Dzieciatkowska, Elise S Bales, David J Orlicky, Richard M Wright, James L McManaman
KEY POINTS: Xanthine oxidoreductase (XOR) modulates milk lipid secretion and lactation initiation. XOR is required for butyrophilin1a1 clustering in the membrane during milk lipid secretion. XOR mediates apical membrane reorganization during milk lipid secretion. Loss of XOR delays milk fat globule secretion. XOR loss alters the proteome of milk fat globules. ABSTRACT: Apocrine secretion is utilized by epithelial cells of exocrine glands. These cells bud off membrane-bound particles into the lumen of the gland, losing a portion of the cytoplasm in the secretion product...
October 15, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27271567/hmbpp-analog-prodrugs-bypass-energy-dependent-uptake-to-promote-efficient-btn3a1-mediated-malignant-cell-lysis-by-v%C3%AE-9v%C3%AE-2-t-lymphocyte-effectors
#19
Ashley M Kilcollins, Jin Li, Chia-Hung Christine Hsiao, Andrew J Wiemer
Vγ9Vδ2 effector T cells lyse cells in response to phosphorus-containing small molecules, providing primates a unique route to remove infected or malignant cells. Yet, the triggering mechanisms remain ill defined. We examined lysis mediated by human Vγ9Vδ2 effector T cells in response to the naturally occurring (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) or a synthetic cell-permeable prodrug, bis (pivaloyloxymethyl) (E)-4-hydroxy-3-methyl-but-2-enyl phosphonate. CD27(+)/CD45RA(-) Th1-like effector cells killed K562 target cells through a mechanism that could be enhanced by either compound or TCR Ab and blocked by Src inhibition or butyrophilin 3 isoform A1 (BTN3A1) disruption...
July 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27210746/rhob-mediates-phosphoantigen-recognition-by-v%C3%AE-9v%C3%AE-2%C3%A2-t-cell-receptor
#20
Zsolt Sebestyen, Wouter Scheper, Anna Vyborova, Siyi Gu, Zuzana Rychnavska, Marleen Schiffler, Astrid Cleven, Coraline Chéneau, Martje van Noorden, Cassie-Marie Peigné, Daniel Olive, Robert Jan Lebbink, Rimke Oostvogels, Tuna Mutis, Gerrit Jan Schuurhuis, Erin J Adams, Emmanuel Scotet, Jürgen Kuball
Human Vγ9Vδ2 T cells respond to tumor cells by sensing elevated levels of phosphorylated intermediates of the dysregulated mevalonate pathway, which is translated into activating signals by the ubiquitously expressed butyrophilin A1 (BTN3A1) through yet unknown mechanisms. Here, we developed an unbiased, genome-wide screening method that identified RhoB as a critical mediator of Vγ9Vδ2 TCR activation in tumor cells. Our results show that Vγ9Vδ2 TCR activation is modulated by the GTPase activity of RhoB and its redistribution to BTN3A1...
May 31, 2016: Cell Reports
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