title: Phosphoantigens and butyrophilin 3A1 induce similar intracellular activation signaling in human TCRVγ9+ γδ T lymphocytes.
abstract: Human γδ cells expressing TCRVγ9 are T lymphocytes with great potential for cancer immunotherapy and unconventional pattern of antigen specificity. These HLA-unrestricted lymphocytes are specifically reactive to non-peptide metabolites (phosphoantigens) and to the butyrophilin 3A (BTN3A/CD277) protein. Whether recognition of such highly different structures trigger the same activation signaling pathway remains unclear, however. Here we combined fluorescent cell barcoding and phosphoflow analysis of TCRVγ9(+) T lymphocytes to compare simultaneously the level of several signaling phosphoproteins after activation by phosphoantigen (BrHPP) or by anti-BTN3A (monoclonal antibody 20.1). This approach shows that the same pathways involving ZAP70, PLCγ2, Akt, NFκB p65, MAPK p38 and Erk1, were induced by either of these stimuli. These data strongly suggest the TCRVγ9(+) T lymphocytes detect phosphoantigens and butyrophilin A3 by the same recognition process.
authors.affiliation: INSERM/Unité Mixte de Recherche 1037, Centre Recherche en Cancerologie de Toulouse, Toulouse, France; Université Toulouse III Paul-Sabatier, Toulouse, France; ERL 5294 CNRS, Hôpital Purpan, Toulouse, France; Laboratoire d'Excellence 'TOUCAN', France; Institut Carnot 'CALYM', France; Institut de Recherche Roche, Boulogne Billancourt, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Decaup
authors.affiliation: INSERM/Unité Mixte de Recherche 1037, Centre Recherche en Cancerologie de Toulouse, Toulouse, France; Université Toulouse III Paul-Sabatier, Toulouse, France; ERL 5294 CNRS, Hôpital Purpan, Toulouse, France; Laboratoire d'Excellence 'TOUCAN', France; Institut Carnot 'CALYM', France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Duault
authors.affiliation: INSERM/Unité Mixte de Recherche 1037, Centre Recherche en Cancerologie de Toulouse, Toulouse, France; Université Toulouse III Paul-Sabatier, Toulouse, France; ERL 5294 CNRS, Hôpital Purpan, Toulouse, France; Laboratoire d'Excellence 'TOUCAN', France; Institut Carnot 'CALYM', France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bezombes
authors.affiliation: INSERM/Unité Mixte de Recherche 1037, Centre Recherche en Cancerologie de Toulouse, Toulouse, France; Université Toulouse III Paul-Sabatier, Toulouse, France; ERL 5294 CNRS, Hôpital Purpan, Toulouse, France; Laboratoire d'Excellence 'TOUCAN', France; Institut Carnot 'CALYM', France.
authors.forename: Mary
authors.initials: M
authors.lastname: Poupot
authors.affiliation: Roche SAS, Boulogne Billancourt, France.
authors.forename: Ariel
authors.initials: A
authors.lastname: Savina
authors.affiliation: INSERM/Unité Mixte de Recherche 1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.affiliation: INSERM/Unité Mixte de Recherche 1037, Centre Recherche en Cancerologie de Toulouse, Toulouse, France; Université Toulouse III Paul-Sabatier, Toulouse, France; ERL 5294 CNRS, Hôpital Purpan, Toulouse, France; Laboratoire d'Excellence 'TOUCAN', France; Institut Carnot 'CALYM', France. Electronic address: jean-jacques.fournie@inserm.fr.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D000071797:Butyrophilins; D002460:Cell Line; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D010750:Phosphoproteins / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; C558381:BTN3A1 protein, human; D000071797:Butyrophilins; D010750:Phosphoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta
keywords: Activation; Cell barcoding; Gamma-delta; Phosphoflow cytometry; Signal transduction; T lymphocytes