PMID- 12610307
OWN - NLM
STAT- MEDLINE
DCOM- 20030314
LR  - 20171116
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Linking)
VI  - 299
IP  - 5611
DP  - 2003 Feb 28
TI  - Activation of lysosomal function during dendritic cell maturation.
PG  - 1400-3
AB  - In response to a variety of stimuli, dendritic cells (DCs) transform from 
      immature cells specialized for antigen capture into mature cells specialized for 
      T cell stimulation. During maturation, the DCs acquire an enhanced capacity to 
      form and accumulate peptide-MHC (major histocompatibility complex) class II 
      complexes. Here we show that a key mechanism responsible for this alteration was 
      the generalized activation of lysosomal function. In immature DCs, internalized 
      antigens were slowly degraded and inefficiently used for peptide loading. 
      Maturation induced activation of the vacuolar proton pump that enhanced lysosomal 
      acidification and antigen proteolysis, facilitating efficient formation of 
      peptide-MHC class II complexes. Lysosomal function in DCs thus appears to be 
      specialized for the developmentally regulated processing of internalized 
      antigens.
FAU - Trombetta, E Sergio
AU  - Trombetta ES
AD  - Department of Cell Biology and Department of Immunobiology, Ludwig Institute for 
      Cancer Research, Yale University School of Medicine, 333 Cedar Street, Post 
      Office Box 208002, New Haven, CT 06520-8002, USA.
FAU - Ebersold, Melanie
AU  - Ebersold M
FAU - Garrett, Wendy
AU  - Garrett W
FAU - Pypaert, Marc
AU  - Pypaert M
FAU - Mellman, Ira
AU  - Mellman I
LA  - eng
GR  - R37-AI34098/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (I-Ak antigen)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Protein Subunits)
RN  - 0 (Tetanus Toxoid)
RN  - 0 (fluorescein isothiocyanate bovine serum albumin)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 1.11.1.- (Horseradish Peroxidase)
RN  - EC 3.2.1.- (hen egg lysozyme)
RN  - EC 3.2.1.17 (Muramidase)
RN  - EC 3.4.- (Cathepsins)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.22.- (asparaginyl endopeptidase, lysosomal)
RN  - EC 3.6.1.- (Vacuolar Proton-Translocating ATPases)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
SB  - IM
MH  - Animals
MH  - *Antigen Presentation
MH  - Cathepsins/metabolism
MH  - Cells, Cultured
MH  - Cysteine Endopeptidases/metabolism
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Enzyme Activation
MH  - Fluorescein-5-isothiocyanate/*analogs & derivatives/metabolism
MH  - Histocompatibility Antigens Class II/immunology/metabolism
MH  - Horseradish Peroxidase/immunology/metabolism
MH  - Hydrogen-Ion Concentration
MH  - Lipopolysaccharides/immunology
MH  - Lysosomes/enzymology/*metabolism
MH  - Mice
MH  - Muramidase/immunology/metabolism
MH  - Ovalbumin/metabolism
MH  - Protein Subunits
MH  - Serum Albumin, Bovine/immunology/metabolism
MH  - Tetanus Toxoid/metabolism
MH  - Vacuolar Proton-Translocating ATPases/metabolism
EDAT- 2003/03/01 04:00
MHDA- 2003/03/15 04:00
CRDT- 2003/03/01 04:00
PHST- 2003/03/01 04:00 [pubmed]
PHST- 2003/03/15 04:00 [medline]
PHST- 2003/03/01 04:00 [entrez]
AID - 299/5611/1400 [pii]
AID - 10.1126/science.1080106 [doi]
PST - ppublish
SO  - Science. 2003 Feb 28;299(5611):1400-3. doi: 10.1126/science.1080106.