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Science. 2003 Mar 21;299(5614):1859-63.

Signaling life and death in the thymus: timing is everything.

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  • 1Laboratory of Transplantation Immunology and Nephrology, Department of Research, University Hospital-Basel, CH-4031 Basel, Switzerland.


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.

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