Activation of Cdk2 is a requirement for antigen-mediated thymic negative selection.
Apoptosis plays a critical role in T cell development and thymic selection. Thymocytes which undergo antigen-induced negative selection have been demonstrated to die by apoptosis. Despite this, relatively little is known about the specific apoptotic pathway involved in negative selection. We have examined the role of cyclin-dependent kinase 2 (Cdk2), a key regulator of thymocyte apoptosis, in this process. Stimulation of thymocytes with cognate antigen leads to a large increase in Cdk2 kinase activity. We also show that pharmacological inhibitors of Cdk2 block thymocyte apoptosis in response to antigen. Our data show that Cdk2 activity is essential for the apoptotic pathway used in negative selection.
Williams
O
O
Division of Molecular Immunology, MRC National Institute for Medical Research, London, GB.
Gil-Gómez
G
G
Norton
T
T
Kioussis
D
D
Brady
H J
HJ
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D042846:CDC2-CDC28 Kinases; D002454:Cell Differentiation / Q000276:immunology; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases