title: Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset.
abstract: Human peripheral Vγ9Vδ2 T cells are activated by phosphorylated metabolites (phosphoagonists [PAg]) of the mammalian mevalonate or the microbial desoxyxylulose-phosphate pathways accumulated by infected or metabolically distressed cells. The underlying mechanisms are unknown. We show that treatment of nonsusceptible target cells with antibody 20.1 against CD277, a member of the extended B7 superfamily related to butyrophilin, mimics PAg-induced Vγ9Vδ2 T-cell activation and that the Vγ9Vδ2 T-cell receptor is implicated in this effect. Vγ9Vδ2 T-cell activation can be abrogated by exposing susceptible cells (tumor and mycobacteria-infected cells, or aminobisphosphonate-treated cells with up-regulated PAg levels) to antibody 103.2 against CD277. CD277 knockdown and domain-shuffling approaches confirm the key implication of the CD277 isoform BTN3A1 in PAg sensing by Vγ9Vδ2 T cells. Fluorescence recovery after photobleaching (FRAP) experiments support a causal link between intracellular PAg accumulation, decreased BTN3A1 membrane mobility, and ensuing Vγ9Vδ2 T-cell activation. This study demonstrates a novel role played by B7-like molecules in human γδ T-cell antigenic activation and paves the way for new strategies to improve the efficiency of immunotherapies using Vγ9Vδ2 T cells.
authors: Inserm, U892, F-44000, Nantes, France.
authors: Christelle
authors: C
authors: Harly
authors: Yves
authors: Y
authors: Guillaume
authors: Steven
authors: S
authors: Nedellec
authors: Cassie-Marie
authors: CM
authors: Peigné
authors: Hannu
authors: H
authors: Mönkkönen
authors: Jukka
authors: J
authors: Mönkkönen
authors: Jianqiang
authors: J
authors: Li
authors: Jürgen
authors: J
authors: Kuball
authors: Erin J
authors: EJ
authors: Adams
authors: Sonia
authors: S
authors: Netzer
authors: Julie
authors: J
authors: Déchanet-Merville
authors: Alexandra
authors: A
authors: Léger
authors: Thomas
authors: T
authors: Herrmann
authors: Richard
authors: R
authors: Breathnach
authors: Daniel
authors: D
authors: Olive
authors: Marc
authors: M
authors: Bonneville
authors: Emmanuel
authors: E
authors: Scotet
mesh_terms: D019138:Antibodies, Blocking; D055910:Antibodies, Immobilized; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000378:metabolism*; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071797:Butyrophilins; D002478:Cells, Cultured; D002999:Clone Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; D055910:Antibodies, Immobilized; D000911:Antibodies, Monoclonal; D000941:Antigens; D015703:Antigens, CD; C558381:BTN3A1 protein, human; D000071797:Butyrophilins; D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins