NEW T CELL SIGNALING · New T cell signaling pathways.

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Project objective

In the immune system, T cells develop their antigen-specificity in the thymus by acquiring a functional T cell receptor (TCR) which triggers intracellular signalling regulating selection, activation and proliferation. The adaptor molecule LAT is functioning as a scaffold protein in a key signalling node of the T cell receptor signalling pathway. Accordingly, mice deficient for LAT or expressing loss-of-function LAT mutants show a dramatic impairment in T cell development. Surprisingly, when a constitutively active form of the tyrosine kinase Lck is expressed in those LAT mutants, the block in T cell development is reverted and some mature T cells are produced, bypassing the need for LAT. Therefore, the first objective of this proposal is to elucidate new LAT-independent pathways used during T cell development by a differential proteomic approach. Various loss-of-function LAT mutations have also been shown to differentially affect alpha-beta versus gamma-delta T cell development.To better understand the parallel development of those two T cell populations, the second objective of this proposal is to follow the early steps of alpha-beta T cells development by tagging the nucleus of beta-chain-expressing cells with a red-fluorescent protein. This will allow in vivo monitoring of alpha-beta T cells in the thymus and in peripheral tissues simultaneously to gamma-delta T cells which are tagged in green in a mouse model engineered in Bernard Malissenas laboratory. Being a Canadian woman with an excellent background in biochemistry, enzymology, apoptotic processes and brain development, joining the laboratory of Bernard Malissen, a world leading group in in vivo studies of the immune system, will favour knowledge and technical transfer in both directions as well as the development of new research tools. This exchange will contribute to promote excellence in European research and international collaboration.

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Participants

• CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE · PARISCoordinatorFrance

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