A Genome-wide Multidimensional RNAi Screen Reveals Pathways Controlling MHC Class II Antigen Presentation

作者：Paul Petra; van den Hoorn Tineke; Jongsma Marlieke L M; Bakker Mark J; Hengeveld Rutger; Janssen Lennert; Cresswell Peter; Egan David A; van Ham Marieke; ten Brinke Anja; Ovaa Huib; Beijer**ergen Roderick L; Kuijl Coenraad^*; Neefjes Jacques

来源：Cell, 2011, 145(2): 268-283.

DOI：10.1016/j.cell.2011.03.023

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 TGF beta. 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.

• 出版日期2011-4-15