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Butyrophilin

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https://www.readbyqxmd.com/read/29197592/porcine-enterocyte-protein-btnl5-negatively-regulates-nf-kappa-b-pathway-by-interfering-p65-nuclear-translocation
#1
Qi Bao, Chong Li, Chongfeng Xu, Ruiying Zhang, Kai Zhao, Ziyuan Duan
Porcine butyrophilin-like 5 (Btnl5) is a novel member of the butyrophilin family, which consists of immune regulators. The expression pattern and the function of this gene remain unclear. In this study, Btnl5 is identified as a negative regulator of the NF-κB pathway. Our study indicates that Btnl5 is mainly expressed in intestinal epithelial cells (IECs) and expressed in membrane systems. Btnl5 inhibits MyD88-mediated activation of the NF-κB pathway. Btnl5 interacts with TNF receptor-associated factor 2 (TRAF2) and transcription factor p65...
November 29, 2017: Gene
https://www.readbyqxmd.com/read/28947936/mixed-aryl-phosphonate-prodrugs-of-a-butyrophilin-ligand
#2
Benjamin J Foust, Michael M Poe, Nicholas A Lentini, Chia-Hung Christine Hsiao, Andrew J Wiemer, David F Wiemer
Studies of aryl phosphonate derivatives of a butyrophilin 3A1 ligand have resulted in identification of a potent stimulant of Vγ9 Vδ2 T cells. This compound, a mixed ester bearing one pivaloyloxymethyl substituent and one 1-naphthyl ester displayed an EC50 of 0.79 nM as a stimulant of T cell proliferation, and a 9.0 nM EC50 in an assay designed to measure interferon gamma production. In both assays, this is the most potent butyrophilin ligand prodrug yet reported, and thus it should be a valuable tool for studies of T cell function...
September 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28920588/%C3%AE-%C3%AE-t-cells-in-homeostasis-and-host-defence-of-epithelial-barrier-tissues
#3
REVIEW
Morten M Nielsen, Deborah A Witherden, Wendy L Havran
Epithelial surfaces line the body and provide a crucial interface between the body and the external environment. Tissue-resident epithelial γδ T cells represent a major T cell population in the epithelial tissues and are ideally positioned to carry out barrier surveillance and aid in tissue homeostasis and repair. In this Review, we focus on the intraepithelial γδ T cell compartment of the two largest epithelial tissues in the body - namely, the epidermis and the intestine - and provide a comprehensive overview of the crucial contributions of intraepithelial γδ T cells to tissue integrity and repair, host homeostasis and protection in the context of the symbiotic relationship with the microbiome and during pathogen clearance...
December 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28862425/btn3a1-discriminates-%C3%AE-%C3%AE-t-cell-phosphoantigens-from-nonantigenic-small-molecules-via-a-conformational-sensor-in-its-b30-2-domain
#4
Mahboob Salim, Timothy J Knowles, Alfie T Baker, Martin S Davey, Mark Jeeves, Pooja Sridhar, John Wilkie, Carrie R Willcox, Hachemi Kadri, Taher E Taher, Pierre Vantourout, Adrian Hayday, Youcef Mehellou, Fiyaz Mohammed, Benjamin E Willcox
Human Vγ9/Vδ2 T-cells detect tumor cells and microbial infections by recognizing small phosphorylated prenyl metabolites termed phosphoantigens (P-Ag). The type-1 transmembrane protein Butyrophilin 3A1 (BTN3A1) is critical to the P-Ag-mediated activation of Vγ9/Vδ2 T-cells; however, the molecular mechanisms involved in BTN3A1-mediated metabolite sensing are unclear, including how P-Ag's are discriminated from nonantigenic small molecules. Here, we utilized NMR and X-ray crystallography to probe P-Ag sensing by BTN3A1...
September 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28807997/phosphoantigen-induced-conformational-change-of-butyrophilin-3a1-btn3a1-and-its-implication-on-v%C3%AE-9v%C3%AE-2-t-cell-activation
#5
Siyi Gu, Joseph R Sachleben, Christopher T Boughter, Wioletta I Nawrocka, Marta T Borowska, Jeffrey T Tarrasch, Georgios Skiniotis, Benoît Roux, Erin J Adams
Human Vγ9Vδ2 T cells respond to microbial infections as well as certain types of tumors. The key initiators of Vγ9Vδ2 activation are small, pyrophosphate-containing molecules called phosphoantigens (pAgs) that are present in infected cells or accumulate intracellularly in certain tumor cells. Recent studies demonstrate that initiation of the Vγ9Vδ2 T cell response begins with sensing of pAg via the intracellular domain of the butyrophilin 3A1 (BTN3A1) molecule. However, it is unknown how downstream events can ultimately lead to T cell activation...
August 29, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28705810/the-butyrophilin-3a1-intracellular-domain-undergoes-a-conformational-change-involving-the-juxtamembrane-region
#6
Khiem Nguyen, Jin Li, Robbins Puthenveetil, Xiaochen Lin, Michael M Poe, Chia-Hung Christine Hsiao, Olga Vinogradova, Andrew J Wiemer
Small isoprenoid diphosphates, such as (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP), are ligands of the internal domain of BTN3A1. Ligand binding in target cells promotes activation of Vγ9Vδ2 T cells. We demonstrate by small-angle X-ray scattering (SAXS) that HMBPP binding to the internal domain of BTN3A1 induces a conformational change in the position of the B30.2 domain relative to the juxtamembrane (JM) region. To better understand the molecular details of this conformational rearrangement, NMR spectroscopy was used to discover that the JM region interacts with HMBPP, specifically at the diphosphate...
July 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28669030/v%C3%AE-9v%C3%AE-2-t-cell-activation-by-strongly-agonistic-nucleotidic-phosphoantigens
#7
Morgane Moulin, Javier Alguacil, Siyi Gu, Asmaa Mehtougui, Erin J Adams, Suzanne Peyrottes, Eric Champagne
Human Vγ9Vδ2 T cells can sense through their TCR tumor cells producing the weak endogenous phosphorylated antigen isopentenyl pyrophosphate (IPP), or bacterially infected cells producing the strong agonist hydroxyl dimethylallyl pyrophosphate (HDMAPP). The recognition of the phosphoantigen is dependent on its binding to the intracellular B30.2 domain of butyrophilin BTN3A1. Most studies have focused on pyrophosphate phosphoantigens. As triphosphate nucleotide derivatives are naturally co-produced with IPP and HDMAPP, we analyzed their specific properties using synthetic nucleotides derived from HDMAPP...
December 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28649364/immunosurveillance-by-human-%C3%AE-%C3%AE-t-lymphocytes-the-emerging-role-of-butyrophilins
#8
REVIEW
Dieter Kabelitz, Marcus Lettau, Ottmar Janssen
In contrast to conventional T lymphocytes, which carry an αβ T-cell receptor and recognize antigens as peptides presented by major histocompatibility complex class I or class II molecules, human γδ T cells recognize different metabolites such as non-peptidic pyrophosphate molecules that are secreted by microbes or overproduced by tumor cells. Hence, γδ T cells play a role in immunosurveillance of infection and cellular transformation. Until recently, it has been unknown how the γδ T-cell receptor senses such pyrophosphates in the absence of known antigen-presenting molecules...
2017: F1000Research
https://www.readbyqxmd.com/read/28631855/a-photo-crosslinkable-biotin-derivative-of-the-phosphoantigen-e-4-hydroxy-3-methylbut-2-enyl-diphosphate-hmbpp-activates-v%C3%AE-9v%C3%AE-2-t-cells-and-binds-to-the-hmbpp-site-of-btn3a1
#9
Andrea Mattarei, Monika Enzinger, Siyi Gu, Mohindar Murugesh Karunakaran, Brigitte Kimmel, Nicole Berner, Erin J Adams, Thomas Herrmann, Sabine Amslinger
Vγ9Vδ2 T cells play an important role in the cross talk of the innate and adaptive immune system. For their activation by phosphoantigens (PAgs), both cell surface receptors, the eponymous Vγ9Vδ2 T cell antigen receptors (Vγ9Vδ2 TCRs) on Vγ9Vδ2 T cells and butyrophilin 3A1 (BTN3A1) on the phosphoantigen-"presenting" cell, are mandatory. To find yet undetected but further contributing proteins, a biotinylated, photo-crosslinkable benzophenone probe BioBP-HMBPP (2) was synthesized from a known allyl alcohol in nine steps and overall 16 % yield...
June 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28620248/relative-gene-expression-of-fatty-acid-synthesis-genes-at-60-days-postpartum-in-bovine-mammary-epithelial-cells-of-surti-and-jafarabadi-buffaloes
#10
Mamta Janmeda, Vishnu Kharadi, Gaurav Pandya, Balkrishna Brahmkshtri, Umed Ramani, Kuldeep Tyagi
AIM: Aim of the study was to study the relative gene expression of genes associated with fatty acid synthesis at 60 days postpartum (pp) in bovine mammary epithelial cells (MECs) of Surti and Jafarabadi buffaloes. MATERIALS AND METHODS: A total of 10 healthy Surti and Jafarabadi buffaloes of each breed were selected at random from Livestock Research Station, Navsari and Cattle Breeding Farm, Junagadh, Gujarat, respectively, for this study. Milk sample was collected from each selected buffalo at day 60 pp from these two breeds to study relative gene expression of major milk fat genes using non-invasive approach of obtaining primary bovine MECs (pBMEC) from milk samples...
May 2017: Veterinary World
https://www.readbyqxmd.com/read/28597565/btn3a1-antibodies-and-phosphoantigens-tcrv%C3%AE-9v%C3%AE-2-see-the-difference
#11
Don-Marc Franchini, Marie Michelas, Olivia Lanvin, Mary Poupot, Jean Jacques Fournié
Human blood γδ T lymphocytes express TCRVγ9Vδ2 and respond to nonpeptide phosphoantigens (PAgs) by a mysterious mechanism involving the BTN3A1 (CD277) molecule . BTN3A1 is a butyrophilin-like protein related to CD80, PD-L1, and MHC, and is either a presenting or a co-stimulatory molecule for PAgs. Although the precise roles and molecular interactions with the TCRVγ9Vδ2 are currently not determined, it is commonly thought that all TCRVγ9Vδ2 lymphocytes 'see' PAg and BTN3A1 together, presumably in a single molecular recognition event...
June 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28580927/the-atp-binding-cassette-transporter-a1-regulates-phosphoantigen-release-and-v%C3%AE-9v%C3%AE-2-t-cell-activation-by-dendritic-cells
#12
Barbara Castella, Joanna Kopecka, Patrizia Sciancalepore, Giorgia Mandili, Myriam Foglietta, Nico Mitro, Donatella Caruso, Francesco Novelli, Chiara Riganti, Massimo Massaia
Vγ9Vδ2 T cells are activated by phosphoantigens, such as isopentenyl pyrophosphate (IPP), which is generated in the mevalonate pathway of antigen-presenting cells. IPP is released in the extracellular microenvironment via unknown mechanisms. Here we show that the ATP-binding cassette transporter A1 (ABCA1) mediates extracellular IPP release from dendritic cells (DC) in cooperation with apolipoprotein A-I (apoA-I) and butyrophilin-3A1. IPP concentrations in the supernatants are sufficient to induce Vγ9Vδ2 T cell proliferation after DC mevalonate pathway inhibition with zoledronic acid (ZA)...
June 5, 2017: Nature Communications
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
#13
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...
June 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
#14
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
#15
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 (PAgs)-like HMBPP ((E)-4-hydroxy-3-methyl-but-2-enyl diphosphate) and butyrophilin 3 (BTN3A, CD277)-specific monoclonal antibody 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 (sc) derivative. All transductants responded readily to PAg but only TCR MOP γ-chain-expressing cells responded to mAb/sc 20...
June 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
#16
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...
June 2017: Immunogenetics
https://www.readbyqxmd.com/read/28246015/exome-array-analysis-identifies-variants-in-spocd1-and-btn3a2-that-affect-risk-for-gastric-cancer
#17
MULTICENTER STUDY
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 cases of gastric cancer. 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...
June 2017: Gastroenterology
https://www.readbyqxmd.com/read/28218845/phosphinophosphonates-and-their-tris-pivaloyloxymethyl-prodrugs-reveal-a-negatively-cooperative-butyrophilin-activation-mechanism
#18
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 23, 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
#19
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
#20
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
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