A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation.
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Paul P, van den Hoorn T, Jongsma ML, Bakker MJ, Hengeveld R, Janssen L, Cresswell P, Egan DA, van Ham M, Ten Brinke A, Ovaa H, Beijersbergen RL, Kuijl C, Neefjes J
A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation.
Cell. 2011 Apr 15;145(2):268-83. doi: 10.1016/j.cell.2011.03.023. Epub 2011 Mar 31.
- PubMed ID
- 21458045 [ View in PubMed]
- 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 TGFbeta. 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.