Signaling life and death in the thymus: timing is everything.
T lymphocytes are generated in the thymus, where developing thymocytes must accept one of two fates: They either differentiate or they die. These fates are chiefly determined by signals that originate from the T cell receptor (TCR), a single receptor complex with a remarkable capacity to decide between distinct cell fates. This review explores TCR signaling in thymocytes and focuses on the kinetic aspects of ligand binding, coreceptor involvement, protein phosphorylation, and mitogen-activated protein kinase (MAPK) activation. Understanding the logic of TCR signaling may eventually explain how thymocytes and T cells distinguish self from nonself, a phenomenon that has fascinated immunologists for 50 years.
Werlen
Guy
G
Laboratory of Transplantation Immunology and Nephrology, Department of Research, University Hospital-Basel, CH-4031 Basel, Switzerland. guy.werlen@unibas.ch
Hausmann
Barbara
B
Naeher
Dieter
D
Palmer
Ed
E
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D004789:Enzyme Activation; D006801:Humans; D008024:Ligands; D020935:MAP Kinase Signaling System; D008285:Major Histocompatibility Complex / Q000276:immunology; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D012641:Selection, Genetic; D017634:Self Tolerance; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
D048868:Adaptor Proteins, Signal Transducing; D000941:Antigens; D015703:Antigens, CD; D002352:Carrier Proteins; C110810:LAT protein, human; D008024:Ligands; D008565:Membrane Proteins; D010750:Phosphoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020928:Mitogen-Activated Protein Kinases