Signaling through MHC class II molecules blocks CD95-induced apoptosis.
B cells are induced to express CD95 upon interaction with T cells. This interaction renders the B cells sensitive to CD95-mediated apoptosis, but ligation of proviability surface receptors is able to inhibit apoptosis induction. MHC class II is a key molecule required for Ag presentation to Th cells, productive T cell-B cell interaction, and B cell activation. We demonstrate here for the first time that MHC class II ligation also confers a rapid resistance to CD95-induced apoptosis, an affect that does not require de novo protein synthesis. Signaling through class II molecules blocks the activation of caspase 8, but does not affect the association of CD95 and Fas-associated death domain-containing protein. MHC class II ligation thus blocks proximal signaling events in the CD95-mediated apoptotic pathway.
Catlett
I M
IM
Department of Microbiology, University of Iowa, and Veterans Affairs Medical Center, Iowa City, IA 52242, USA.
Xie
P
P
Hostager
B S
BS
Bishop
G A
GA
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D053200:Fas-Associated Death Domain Protein; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006868:Hydrolysis; D051379:Mice; D008807:Mice, Inbred BALB C; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D061945:Caspase Inhibitors; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D000949:Histocompatibility Antigens Class II; D011506:Proteins; D019014:fas Receptor; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases