A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation.
Cell
; 145(2): 268-83, 2011 Apr 15.
Article
in En
| MEDLINE
| ID: mdl-21458045
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 TGFß. 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histocompatibility Antigens Class II
/
Antigen Presentation
/
Genome-Wide Association Study
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Cell
Year:
2011
Document type:
Article
Affiliation country: