title: A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation.
abstract: MHC class II molecules (MHC-II) present peptides to T helper cells to facilitate immune responses and are strongly linked to autoimmune diseases. To unravel processes controlling MHC-II antigen presentation, we performed a genome-wide flow cytometry-based RNAi screen detecting MHC-II expression and peptide loading followed by additional high-throughput assays. All data sets were integrated to answer two fundamental questions: what regulates tissue-specific MHC-II transcription, and what controls MHC-II transport in dendritic cells? MHC-II transcription was controlled by nine regulators acting in feedback networks with higher-order control by signaling pathways, including TGFβ. MHC-II transport was controlled by the GTPase ARL14/ARF7, which recruits the motor myosin 1E via an effector protein ARF7EP. This complex controls movement of MHC-II vesicles along the actin cytoskeleton in human dendritic cells (DCs). These genome-wide systems analyses have thus identified factors and pathways controlling MHC-II transcription and transport, defining targets for manipulation of MHC-II antigen presentation in infection and autoimmunity.
authors: Division of Cell Biology and Centre for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors: Petra
authors: P
authors: Paul
authors: Tineke
authors: T
authors: van den Hoorn
authors: Marlieke L M
authors: ML
authors: Jongsma
authors: Mark J
authors: MJ
authors: Bakker
authors: Rutger
authors: R
authors: Hengeveld
authors: Lennert
authors: L
authors: Janssen
authors: Peter
authors: P
authors: Cresswell
authors: David A
authors: DA
authors: Egan
authors: Marieke
authors: M
authors: van Ham
authors: Anja
authors: A
authors: Ten Brinke
authors: Huib
authors: H
authors: Ovaa
authors: Roderick L
authors: RL
authors: Beijersbergen
authors: Coenraad
authors: C
authors: Kuijl
authors: Jacques
authors: J
authors: Neefjes
mesh_terms: D000199:Actins / Q000378:metabolism; D017951:Antigen Presentation; D015551:Autoimmunity; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D055106:Genome-Wide Association Study; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D009218:Myosins / Q000378:metabolism; D034622:RNA Interference
chemical_list: D000199:Actins; D000949:Histocompatibility Antigens Class II; D009218:Myosins