PMID- 11975981
OWN - NLM
STAT- MEDLINE
DCOM- 20021009
LR  - 20190906
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 63
IP  - 5
DP  - 2002 May
TI  - HLA class II signals sensitize B lymphocytes to apoptosis via Fas/CD95 by 
      increasing FADD recruitment to activated Fas and activation of caspases.
PG  - 375-83
AB  - Human leukocyte antigen (HLA) class II heterodimers have a well defined role in 
      peptide presentation to helper T lymphocytes. Moreover, engagement of HLA class 
      II molecules leads to signal transduction in the antigen presenting cell. 
      Signaling via HLA-DR increases CD95 mediated hypoploidy in B-cell blasts. Given 
      the importance of CD95 for the homeostasis of lymphocyte populations, we examined 
      the impact of the HLA-DR signal on the most proximal events in the CD95 apoptotic 
      pathway. CD95 activation recruits the adapter molecule Fas-associated death 
      domain protein (FADD) and thereby provides a scaffold for procaspase-8 
      activation. The HLA-DR signal increased both recruitment of FADD and activation 
      of caspases-3 and -8 via CD95 activation. Sensitization was tightly controlled 
      because neither FADD recruitment to CD95 nor caspase activation was induced via 
      HLA-DR alone. In contrast, the HLA-DR signal and the CD95 signal both led to 
      decreased mitochondrial membrane potential. Taken together, these data indicate 
      that ligand interaction with HLA class II molecules preactivates the antigen 
      presenting cell for death in the event of a subsequent interaction with the CD95 
      ligand. This would ensure termination of a specific immune response, particularly 
      in cells with limited sensitivity to CD95 mediated apoptosis alone.
FAU - Blancheteau, Vincent
AU  - Blancheteau V
AD  - INSERM U396, Immunogenetique Humaine, Institut Biomedical des Cordeliers, Paris, 
      France.
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  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Epitopes)
RN  - 0 (FADD protein, human)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (fas Receptor)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - *Apoptosis
MH  - B-Lymphocytes/cytology/*immunology
MH  - Carrier Proteins/*metabolism/physiology
MH  - Caspase 3
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/*metabolism/physiology
MH  - Cells, Cultured
MH  - Enzyme Activation
MH  - Epitopes/immunology
MH  - Fas-Associated Death Domain Protein
MH  - Flow Cytometry
MH  - Genes, MHC Class II
MH  - Histocompatibility Antigens Class II/*physiology
MH  - Humans
MH  - Lymphocyte Activation
MH  - Membrane Potentials
MH  - Mitochondria/physiology
MH  - Ploidies
MH  - Protein Transport
MH  - *Signal Transduction
MH  - fas Receptor/*physiology
EDAT- 2002/04/27 10:00
MHDA- 2002/10/10 04:00
CRDT- 2002/04/27 10:00
PHST- 2002/04/27 10:00 [pubmed]
PHST- 2002/10/10 04:00 [medline]
PHST- 2002/04/27 10:00 [entrez]
AID - S0198885902003841 [pii]
AID - 10.1016/s0198-8859(02)00384-1 [doi]
PST - ppublish
SO  - Hum Immunol. 2002 May;63(5):375-83. doi: 10.1016/s0198-8859(02)00384-1.