PMID- 23200228
OWN - NLM
STAT- MEDLINE
DCOM- 20130617
LR  - 20130329
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 55
IP  - 2
DP  - 2013 Sep
TI  - How to target MHC class II into the MIIC compartment.
PG  - 162-5
LID - S0161-5890(12)00436-1 [pii]
LID - 10.1016/j.molimm.2012.10.022 [doi]
AB  - Major histocompatibility complex (MHC) class II molecules (MHC II) present 
      exogenous antigens to CD4+ T cells to modulate immune responses. To contact these 
      antigens, MHC II is delivered to the late endosomal MHC class II compartment 
      (MIIC). This compartment has a complex architecture and consists of internal 
      membranes or vesicles surrounded by a limiting membrane. These subdomains have 
      different protein and lipid content. Also MHC II peptide loading is spatially 
      organized in MIIC as it interacts with DM on intralumenal vesicles (ILVs) to bind 
      antigen. How this is controlled is only understood in a sketchy manner. This may 
      involve ubiquitin modification of MHC II, possibly by E3 ligases of the March 
      family. But other proteins are likely involved as well including E3 ligases, 
      deubiquitylating enzymes (DUBs), adaptor, scaffold, motor and vesicular coat 
      proteins. Our lab performed a genome-wide siRNA screen to define novel proteins 
      and pathways involved in MHC II antigen presentation. The data set is used to 
      select candidate proteins involved in targeting MHC II into MIIC. This process 
      involves ubiquitin modifications and various new molecules not considered as yet 
      in this complex pathway. These molecules may be targeted by drugs to manipulate 
      MHC II responses in auto-immunity, transplantation and other disease states.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Garstka, Malgorzata A
AU  - Garstka MA
AD  - Netherlands Cancer Institute, Amsterdam, The Netherlands. m.garstka@nki.nl
FAU - Neefjes, Jacques
AU  - Neefjes J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20121127
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - *Antigen Presentation
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Endosomes/*immunology/metabolism/ultrastructure
MH  - Genome-Wide Association Study
MH  - Histocompatibility Antigens Class II/*immunology
MH  - Humans
MH  - RNA Interference
MH  - RNA, Small Interfering
EDAT- 2012/12/04 06:00
MHDA- 2013/06/19 06:00
CRDT- 2012/12/04 06:00
PHST- 2012/10/03 00:00 [received]
PHST- 2012/10/07 00:00 [accepted]
PHST- 2012/12/04 06:00 [entrez]
PHST- 2012/12/04 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
AID - S0161-5890(12)00436-1 [pii]
AID - 10.1016/j.molimm.2012.10.022 [doi]
PST - ppublish
SO  - Mol Immunol. 2013 Sep;55(2):162-5. doi: 10.1016/j.molimm.2012.10.022. Epub 2012 
      Nov 27.