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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Antigen Presentation*
  • Autoimmunity
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Genome-Wide Association Study*
  • Histocompatibility Antigens Class II / immunology*
  • Humans
  • Myosins / metabolism
  • RNA Interference


  • Actins
  • Histocompatibility Antigens Class II
  • Myosins