title: Butyrophilin 3A1 binds phosphorylated antigens and stimulates human γδ T cells.
abstract: Human T cells that express a T cell antigen receptor (TCR) containing γ-chain variable region 9 and δ-chain variable region 2 (Vγ9Vδ2) recognize phosphorylated prenyl metabolites as antigens in the presence of antigen-presenting cells but independently of major histocompatibility complex (MHC), the MHC class I-related molecule MR1 and antigen-presenting CD1 molecules. Here we used genetic approaches to identify the molecule that binds and presents phosphorylated antigens. We found that the butyrophilin BTN3A1 bound phosphorylated antigens with low affinity, at a stoichiometry of 1:1, and stimulated mouse T cells with transgenic expression of a human Vγ9Vδ2 TCR. The structures of the BTN3A1 distal domain in complex with host- or microbe-derived phosphorylated antigens had an immunoglobulin-like fold in which the antigens bound in a shallow pocket. Soluble Vγ9Vδ2 TCR interacted specifically with BTN3A1-antigen complexes. Accordingly, BTN3A1 represents an antigen-presenting molecule required for the activation of Vγ9Vδ2 T cells.
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vavassori
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Gan Siok
authors.initials: GS
authors.lastname: Wan
authors.forename: Gundimeda S
authors.initials: GS
authors.lastname: Ramanjaneyulu
authors.forename: Marco
authors.initials: M
authors.lastname: Cavallari
authors.forename: Sary
authors.initials: S
authors.lastname: El Daker
authors.forename: Travis
authors.initials: T
authors.lastname: Beddoe
authors.forename: Alex
authors.initials: A
authors.lastname: Theodossis
authors.forename: Neal K
authors.initials: NK
authors.lastname: Williams
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Dinish U
authors.initials: DU
authors.lastname: Soudamini
authors.forename: Kong Kien
authors.initials: KK
authors.lastname: Voon
authors.forename: Malini
authors.initials: M
authors.lastname: Olivo
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Lucia
authors.initials: L
authors.lastname: Mori
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000276:immunology* / Q000378:metabolism*; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071797:Butyrophilins; D002896:Chromosomes, Human, Pair 6; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D010755:Organophosphates / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: C467061:4-hydroxy-3-methyl-2-butenyl diphosphate; D000941:Antigens; D015703:Antigens, CD; C558381:BTN3A1 protein, human; D000071797:Butyrophilins; D010755:Organophosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta