title: Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes.
abstract: Evidence has recently emerged that butyrophilins, which are members of the extended B7 family of co-stimulatory molecules, have diverse functions in the immune system. We found that the human and mouse genes encoding butyrophilin-2A2 (BTN2A2) are regulated by the class II trans-activator and regulatory factor X, two transcription factors dedicated to major histocompatibility complex class II expression, suggesting a role in T cell immunity. To address this, we generated Btn2a2-deficient mice. Btn2a2(-/-) mice exhibited enhanced effector CD4(+) and CD8(+) T cell responses, impaired CD4(+) regulatory T cell induction, potentiated antitumor responses, and exacerbated experimental autoimmune encephalomyelitis. Altered immune responses were attributed to Btn2a2 deficiency in antigen-presenting cells rather than T cells or nonhematopoietic cells. These results provide the first genetic evidence that BTN2A2 is a co-inhibitory molecule that modulates T cell-mediated immunity.
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Sarter
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Leimgruber
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Gobet
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Vishal
authors.initials: V
authors.lastname: Agrawal
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dunand-Sauthier
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Emmanuèle
authors.initials: E
authors.lastname: Barras
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland Department of Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Béatris
authors.initials: B
authors.lastname: Mastelic-Gavillet
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland Department of Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Arun
authors.initials: A
authors.lastname: Kamath
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland Department of Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Paola
authors.initials: P
authors.lastname: Fontannaz
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Leslie
authors.initials: L
authors.lastname: Guéry
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Fernanda do Valle
authors.initials: Fdo V
authors.lastname: Duraes
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Carla
authors.initials: C
authors.lastname: Lippens
authors.affiliation: Novimmune SA, 1228 Plan-les-Ouates, Switzerland.
authors.forename: Ulla
authors.initials: U
authors.lastname: Ravn
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Santiago-Raber
authors.affiliation: Novimmune SA, 1228 Plan-les-Ouates, Switzerland.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Magistrelli
authors.affiliation: Novimmune SA, 1228 Plan-les-Ouates, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fischer
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland Department of Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Hugues
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland walter.reith@unige.ch.
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000071797:Butyrophilins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006801:Humans; D007111:Immunity, Cellular; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: C000605700:BTN2A2 protein, human; D000071797:Butyrophilins; D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; C083728:MHC class II transactivator protein; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors
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