MRC National Institute for Medical Research, London
Science for Health
Benedict Seddon group project:
Control of T cell homeostasis by Zap70 dependent TCR signalling
TCR signalling regulates T cell homeostasis throughout T cell ontogeny. The peripheral repertoire is shaped by positive and negative selection in the thymus, and peripheral T cell survival depends upon tonic homeostatic signals from the TCR induced by spMHC complexes on DCs in peripheral lymphoid organs. In order to better understand how TCR signalling regulates T cell homeostasis, we developed a novel mouse model in which the tyrosine kinase Zap70 is conditionally expressed using the tetracycline inducible system. Zap70 is a direct downstream target of Src family kinases and essential for TCR signalling. Consequently, in the absence of Zap70 expression, thymic development is completely arrested and Zap70 deficient mice have no peripheral αβ T cells. Conditional expression of Zap70 therefore allowed us to investigate how TCR signalling regulates T cell homeostasis.
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Kinetics of T cell development following resumption of Zap70 dependent signalling
Selected publications
- Manoj Saini, Charles Sinclair, Daniel Marshall, Mauro Tolaini, Shimon Sakaguchi and Benedict Seddon (2010)
Regulation of Zap70 expression during thymic development allows temporal separation of CD4 and CD8 repertoire selection at different signalling thresholds
Science Signaling in press,
Seddon group
Recent publications
Research projects
- Regulation of naïve and memory T cell homeostasis by IL-7
- Control of T cell homeostasis by Zap70 dependent TCR signalling
- Mathematical modelling of homeostatic responses
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