PMID- 14604956
OWN - NLM
STAT- MEDLINE
DCOM- 20040415
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 6
DP  - 2004 Mar 15
TI  - Dendritic cells constitutively present self antigens in their immature state in 
      vivo and regulate antigen presentation by controlling the rates of MHC class II 
      synthesis and endocytosis.
PG  - 2187-95
AB  - Dendritic cells (DCs) change their antigen-presenting properties during 
      maturation. Immature DCs efficiently capture antigens, but are reported to be 
      impaired in their processing and presenting capacity. Upon an encounter with an 
      inflammatory stimulus, DCs undergo a maturation process that leads to efficient 
      presentation of antigens captured at the time of activation, but precludes 
      processing of antigens encountered at later time points. The mechanisms that 
      underlie these developmental changes are controversial. Thus, it is unclear 
      whether immature DCs can present self antigens, and which are the checkpoints 
      that regulate antigen presentation in immature and mature DCs. We have 
      characterized these mechanisms using DCs derived directly from lymphoid organs. 
      Immature lymphoid organ DCs constitutively presented self peptides bound to major 
      histocompatibility complex class II (MHCII) molecules, but these MHCII-peptide 
      complexes were degraded quickly after their transient expression on the cell 
      surface. During maturation, MHC II endocytosis was down-regulated, so that newly 
      generated MHC II-peptide complexes accumulated on the plasma membrane. 
      Simultaneously, MHC II synthesis was down-regulated, thus preventing the turnover 
      of the MHC II-peptide complexes that accumulated early during maturation. Our 
      results demonstrate that immature DCs constitutively present self antigens in the 
      lymphoid organs and characterize the molecular basis of the capacity of DCs to 
      provide "antigenic memory" in vivo.
FAU - Wilson, Nicholas S
AU  - Wilson NS
AD  - Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 
      Australia.
FAU - El-Sukkari, Dima
AU  - El-Sukkari D
FAU - Villadangos, Jose A
AU  - Villadangos JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031106
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Autoantigens)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/*immunology
MH  - Autoantigens/*immunology/metabolism
MH  - Cell Differentiation/immunology
MH  - Dendritic Cells/*immunology/metabolism
MH  - Down-Regulation/immunology
MH  - Endocytosis/*immunology
MH  - Histocompatibility Antigens Class II/*immunology/metabolism
MH  - Immunologic Memory/immunology
MH  - In Vitro Techniques
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Spleen/cytology
EDAT- 2003/11/08 05:00
MHDA- 2004/04/16 05:00
CRDT- 2003/11/08 05:00
PHST- 2003/11/08 05:00 [pubmed]
PHST- 2004/04/16 05:00 [medline]
PHST- 2003/11/08 05:00 [entrez]
AID - S0006-4971(20)50013-X [pii]
AID - 10.1182/blood-2003-08-2729 [doi]
PST - ppublish
SO  - Blood. 2004 Mar 15;103(6):2187-95. doi: 10.1182/blood-2003-08-2729. Epub 2003 Nov 
      6.