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Different initiation of pre-TCR and γδTCR signalling

Abstract : Lineage choice is of great interest in developmental biology. In the immune system, the alphabeta and gammadelta lineages of T lymphocytes diverge during the course of the beta-, gamma- and delta-chain rearrangement of T-cell receptor (TCR) genes that takes place within the same precursor cell and which results in the formation of the gammadeltaTCR or pre-TCR proteins. The pre-TCR consists of the TCRbeta chain covalently linked to the pre-TCRalpha protein, which is present in immature but not in mature T cells which instead express the TCRalpha chain. Animals deficient in pre-TCRalpha have few alphabeta lineage cells but an increased number of gammadelta T cells. These gammadelta T cells exhibit more extensive TCRbeta rearrangement than gammadelta T cells from wild-type mice. These observations are consistent with the idea that different signals emanating from the gammadeltaTCR and pre-TCR instruct lineage commitment. Here we show, by using confocal microscopy and biochemistry to analyse the initiation of signalling, that the pre-TCR but not the gammadeltaTCR colocalizes with the p56lck Src kinase into glycolipid-enriched membrane domains (rafts) apparently without any need for ligation. This results in the phosphorylation of CD3epsilon and Zap-70 signal transducing molecules. The results indicate clear differences between pre-TCR and gammadeltaTCR signalling.
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Contributor : Claude Saint-Ruf Connect in order to contact the contributor
Submitted on : Monday, July 8, 2019 - 5:37:27 PM
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Claude Saint-Ruf, Maddalena Panigada, Orly Azogui, Pascale Debey, Harald von Boehmer, et al.. Different initiation of pre-TCR and γδTCR signalling. Nature, 2000, 406 (6795), pp.524-527. ⟨10.1038/35020093⟩. ⟨inserm-02177263⟩



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