Obligatory role for cooperative signaling by pre-TCR and notch during thymocyte differentiation

Ciofani, M., Schmitt, T.M., Ciofani, A., Michie, A.M. , Cuburu, N., Aublin, A., Maryanski, J.L. and Zuniga-Pflucker, J.C. (2004) Obligatory role for cooperative signaling by pre-TCR and notch during thymocyte differentiation. Journal of Immunology, 172(9), pp. 5230-5239.

Abstract

The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR-beta gene locus. Notch signaling has been implicated in various stages during T lymphopoiesis. However, it is unclear whether Notch receptor-ligand interactions are necessary during beta selection. Here, we show that pre-TCR signaling concurrent with Notch receptor and Delta-like-1 ligand interactions are required for the survival, proliferation, and differentiation of mouse CD4(-)CD8(-) thymocytes to the CD4(+)CD8(+) stage. Furthermore, we address the minimal signaling requirements underlying beta selection and show a hierarchical positioning of key proximal signaling molecules. Collectively, our results demonstrate an essential role for Notch receptor-ligand interactions in enabling the autonomous signaling capacity of the pre-TCR complex.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Michie, Professor Alison
• Authors: Ciofani, M., Schmitt, T.M., Ciofani, A., Michie, A.M., Cuburu, N., Aublin, A., Maryanski, J.L., and Zuniga-Pflucker, J.C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Immunology
• ISSN: 0022-1767