PMID- 12832441
OWN - NLM
STAT- MEDLINE
DCOM- 20030819
LR  - 20190605
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 74
IP  - 1
DP  - 2003 Jul
TI  - Composition of MHC class II-enriched lipid microdomains is modified during 
      maturation of primary dendritic cells.
PG  - 40-8
AB  - Dendritic cells (DCs) are the most potent antigen presenting cells. Major 
      histocompatibility complex (MHC) class II molecule expression changes with 
      maturation; immature DCs concentrate MHC class II molecules intracellularly, 
      whereas maturation increases surface expression of MHC class II and costimulatory 
      molecules to optimize antigen presentation. Signal transduction via MHC class II 
      molecules localized in lipid microdomains has been described in B lymphocytes and 
      in the THP-1 monocyte cell line. We have characterized MHC class II molecules 
      throughout human DC maturation with particular attention to their localization in 
      lipid-rich microdomains. Only immature DCs expressed empty MHC class II 
      molecules, and maturation increased the level of peptide-bound heterodimers. 
      Ligand binding to surface human leukocyte antigen (HLA)-DR induced rapid 
      internalization in immature DCs. The proportion of cell-surface 
      detergent-insoluble glycosphingolipid-enriched microdomain-clustered HLA-DR was 
      higher in immature DCs despite the higher surface expression of HLA-DR in mature 
      DCs. Constituents of HLA-DR containing microdomains included the src kinase Lyn 
      and the cytoskeletal protein tubulin in immature DCs. Maturation modified the 
      composition of the HLA-DR-containing microdomains to include protein kinase C 
      (PKC)-delta, Lyn, and the cytoskeletal protein actin, accompanied by the loss of 
      tubulin. Signaling via HLA-DR redistributed HLA-DR and -DM and PKC-delta as well 
      as enriching the actin content of mature DC microdomains. The increased 
      expression of HLA-DR as a result of DC maturation was therefore accompanied by 
      modification of the spatial organization of HLA-DR. Such regulation could 
      contribute to the distinct responses induced by ligand binding to MHC class II 
      molecules in immature versus mature DCs.
FAU - Setterblad, Niclas
AU  - Setterblad N
AD  - INSERM U396 and. IDM (Immuno-Designed Molecules), Institut Biomedical des 
      Cordeliers, Paris, France.
FAU - Roucard, Corinne
AU  - Roucard C
FAU - Bocaccio, Claire
AU  - Bocaccio C
FAU - Abastado, Jean-Pierre
AU  - Abastado JP
FAU - Charron, Dominique
AU  - Charron D
FAU - Mooney, Nuala
AU  - Mooney N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Actins)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Peptide Fragments)
RN  - 0 (Tubulin)
RN  - EC 2.7.10.2 (lyn protein-tyrosine kinase)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.13 (PRKCD protein, human)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
SB  - IM
MH  - Actins/analysis
MH  - Dendritic Cells/*cytology/immunology/ultrastructure
MH  - HLA-DR Antigens/analysis/chemistry/metabolism
MH  - Histocompatibility Antigens Class II/*analysis/chemistry/metabolism
MH  - Humans
MH  - Membrane Microdomains/*chemistry/immunology
MH  - Peptide Fragments/metabolism
MH  - Protein Binding
MH  - Protein Kinase C/metabolism
MH  - Protein Kinase C-delta
MH  - Tubulin/analysis
MH  - src-Family Kinases/metabolism
EDAT- 2003/07/02 05:00
MHDA- 2003/08/20 05:00
CRDT- 2003/07/02 05:00
PHST- 2003/07/02 05:00 [pubmed]
PHST- 2003/08/20 05:00 [medline]
PHST- 2003/07/02 05:00 [entrez]
AID - 10.1189/jlb.0103045 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2003 Jul;74(1):40-8. doi: 10.1189/jlb.0103045.