title: Differential role for CD277 as a co-regulator of the immune signal in T and NK cells.
abstract: The human butyrophilin (BTN) 3 or CD277 molecules belong to the B7 family members and are expressed in various immune cells such as T and NK cells. Here, we show that CD277 triggering considerably enhances TCR-induced cytokine production and cell proliferation, even when another co-stimulatory molecule, CD28, is engaged. These CD277-induced additive functional effects are in accordance with the detection of early T-cell activation events such as TCR-induced cell signaling being increased upon CD277 engagement. However, we found that CD277 triggering is not involved in CD16- or NKp46-induced NK cell activation. BTN3/CD277 comprises three structurally related members, BTN3A1, BTN3A2 and BTN3A3. CD277 antibodies recognize all isoforms and we describe a differential expression of BTN3 isoforms between T and NK cells that could explain differential CD277 functions between T and NK cells. Our results show that, while T cells express all BTN3/CD277 transcripts, NK cells express mostly BTN3A2, which lacks the B30.2 intracellular domain. Furthermore, NKp30-induced cytokine production is decreased by the specific engagement of BTN3A2, but not by BTN3A1 triggering. Thus, we provide new insights into the CD277 co-stimulatory pathway that may differentially participate in the regulation of various cell-mediated immune responses.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 891, Centre de Recherche en Cancérologie de Marseille, Marseille, France.
authors.forename: Nassima
authors.initials: N
authors.lastname: Messal
authors.forename: Emilie
authors.initials: E
authors.lastname: Mamessier
authors.forename: Aude
authors.initials: A
authors.lastname: Sylvain
authors.forename: Javier
authors.initials: J
authors.lastname: Celis-Gutierrez
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Thibult
authors.forename: Bruno
authors.initials: B
authors.lastname: Chetaille
authors.forename: Guylène
authors.initials: G
authors.lastname: Firaguay
authors.forename: Sonia
authors.initials: S
authors.lastname: Pastor
authors.forename: Yves
authors.initials: Y
authors.lastname: Guillaume
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Ivan
authors.initials: I
authors.lastname: Hirsch
authors.forename: Jacques A
authors.initials: JA
authors.lastname: Nunès
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000071797:Butyrophilins; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019556:COS Cells; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000276:immunology; D020033:Protein Isoforms; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; C558381:BTN3A1 protein, human; D000071797:Butyrophilins; D018106:CD28 Antigens; D016207:Cytokines; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D020033:Protein Isoforms; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma