Mechanistic basis of pre–T cell receptor–mediated autonomous signaling critical for thymocyte development
- 4 December 2005
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 7 (1) , 67-75
- https://doi.org/10.1038/ni1290
Abstract
The pre–T cell receptor (TCR) is crucial for early T cell development and is proposed to function in a ligand-independent way. However, the molecular mechanism underlying the autonomous signals remains elusive. Here we show that the pre-TCR complex spontaneously formed oligomers. Specific charged residues in the extracellular domain of the pre-TCR α-chain mediated formation of the oligomers in vitro. Alteration of these residues eliminated the ability of the pre-TCR α-chain to support pre-TCR signaling in vivo. Dimerization but not raft localization of CD3ε was sufficient to simulate pre-TCR function and promote β-selection. These results suggest that the pre-TCR complex can deliver its signal autonomously through oligomerization of the pre-TCR α-chain mediated by charged residues.Keywords
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