PMID- 23532855
OWN - NLM
STAT- MEDLINE
DCOM- 20130712
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 19
DP  - 2013 May 10
TI  - Major histocompatibility complex (MHC) class II-peptide complexes arrive at the 
      plasma membrane in cholesterol-rich microclusters.
PG  - 13236-42
LID - 10.1074/jbc.M112.442640 [doi]
AB  - BACKGROUND: Antigen-specific CD4 T cells are activated by small numbers of 
      antigenic peptide-MHC class II (pMHC-II) complexes on dendritic cells (DCs). 
      RESULTS: Newly generated pMHC-II complexes are present in small clusters on the 
      DC surface. CONCLUSION: pMHC-II clusters permit efficient T cell activation. 
      SIGNIFICANCE: The appearance of clustered pMHC-II reveals the organization of the 
      T cell antigen receptor ligand on the DC surface. Dendritic cells (DCs) function 
      by stimulating naive antigen-specific CD4 T cells to proliferate and secrete a 
      variety of immunomodulatory factors. The ability to activate naive T cells comes 
      from the capacity of DCs to internalize, degrade, and express peptide fragments 
      of antigenic proteins on their surface bound to MHC class II molecules (MHC-II). 
      Although DCs express tens of thousands of distinct MHC-II, very small amounts of 
      specific peptide-MHC-II complexes are required to interact with and activate T 
      cells. We now show that stimulatory MHC-II I-A(k)-HEL(46-61) complexes that move 
      from intracellular antigen-processing compartments to the plasma membrane are not 
      randomly distributed on the DC surface. Confocal immunofluorescence microscopy 
      and quantitative immunoelectron microscopy reveal that the majority of newly 
      generated MHC-II I-A(k)-HEL(46-61) complexes are expressed in sub-100-nm 
      microclusters on the DC membrane. These microclusters are stabilized in 
      cholesterol-containing microdomains, and cholesterol depletion inhibits the 
      stability of these clusters as well as the ability of the DCs to function as 
      antigen-presenting cells. These results demonstrate that specific cohorts of 
      peptide-MHC-II complexes expressed on the DC surface are present in 
      cholesterol-dependent microclusters and that cluster integrity is important for 
      antigen-specific naive CD4 T cell activation by DCs.
FAU - Bosch, Berta
AU  - Bosch B
AD  - Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, MD 
      20892, USA.
FAU - Heipertz, Erica L
AU  - Heipertz EL
FAU - Drake, James R
AU  - Drake JR
FAU - Roche, Paul A
AU  - Roche PA
LA  - eng
GR  - R01 AI065773/AI/NIAID NIH HHS/United States
GR  - AI-065773/AI/NIAID NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20130326
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Membrane Lipids)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Antigens/immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cell Membrane/*metabolism
MH  - Cells, Cultured
MH  - Cholesterol/*metabolism
MH  - Dendritic Cells/immunology/metabolism
MH  - Histocompatibility Antigens Class II/*metabolism
MH  - Lymphocyte Activation
MH  - Membrane Lipids/metabolism
MH  - Membrane Microdomains/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Protein Transport
PMC - PMC3650363
OTO - NOTNLM
OT  - Dendritic Cells
OT  - Lipid Raft
OT  - Major Histocompatibility Complex (MHC)
OT  - Membrane Trafficking
OT  - T Cell
EDAT- 2013/03/28 06:00
MHDA- 2013/07/16 06:00
PMCR- 2014/05/10
CRDT- 2013/03/28 06:00
PHST- 2013/03/28 06:00 [entrez]
PHST- 2013/03/28 06:00 [pubmed]
PHST- 2013/07/16 06:00 [medline]
PHST- 2014/05/10 00:00 [pmc-release]
AID - S0021-9258(19)54555-0 [pii]
AID - M112.442640 [pii]
AID - 10.1074/jbc.M112.442640 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 May 10;288(19):13236-42. doi: 10.1074/jbc.M112.442640. Epub 
      2013 Mar 26.