title: RNAi screen for kinases and phosphatases that play a role in antigen presentation by dendritic cells.
abstract: Effective CD8(+)  T-cell responses against tumor or microbial antigens that are not directly expressed in antigen-presenting cells (APCs) depend on the cross-presentation of these antigens on MHC class I in APCs. To identify signaling molecules that regulate cross-presentation, we used lentiviral-based RNA interference to test the roles of hundreds of kinases and phosphatases in this process. Our study uncovered eight previously unknown genes, consisting of one positive and seven negative regulators of antigen cross-presentation. Depletion of Acvr1c, a type I receptor for TGF-β family of signaling molecules, led to an increase in CD80 and CD86 co-stimulator surface expression and secreted IL-12 in mouse bone marrow-derived DCs, as well as antigen-specific T-cell proliferation.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. lmoita@fm.ul.pt
authors.forename: Catarina F
authors.initials: CF
authors.lastname: Moita
authors.forename: Ângelo
authors.initials: Â
authors.lastname: Chora
authors.forename: Nir
authors.initials: N
authors.lastname: Hacohen
authors.forename: Luis F
authors.initials: LF
authors.lastname: Moita
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology*; D005434:Flow Cytometry; D020868:Gene Silencing / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000276:immunology*; D010770:Phosphotransferases / Q000235:genetics / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D034622:RNA Interference / Q000276:immunology
chemical_list: D012313:RNA; D010770:Phosphotransferases; D030201:Activin Receptors, Type I; C515277:Acvr1c protein, mouse; D010744:Phosphoric Monoester Hydrolases