A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation - PubMed (original) (raw)

. 2011 Apr 15;145(2):268-83.

doi: 10.1016/j.cell.2011.03.023. Epub 2011 Mar 31.

Tineke van den Hoorn, Marlieke L M Jongsma, Mark J Bakker, Rutger Hengeveld, Lennert Janssen, Peter Cresswell, David A Egan, Marieke van Ham, Anja Ten Brinke, Huib Ovaa, Roderick L Beijersbergen, Coenraad Kuijl, Jacques Neefjes

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A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation

Petra Paul et al. Cell. 2011.

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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.

Copyright © 2011 Elsevier Inc. All rights reserved.

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