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Publication : Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development.

First Author  Yamasaki S Year  2006
Journal  Nat Immunol Volume  7
Issue  1 Pages  67-75
PubMed ID  16327787 Mgi Jnum  J:112567
Mgi Id  MGI:3662788 Doi  10.1038/ni1290
Citation  Yamasaki S, et al. (2006) Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development. Nat Immunol 7(1):67-75
abstractText  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 alpha-chain mediated formation of the oligomers in vitro. Alteration of these residues eliminated the ability of the pre-TCR alpha-chain to support pre-TCR signaling in vivo. Dimerization but not raft localization of CD3epsilon was sufficient to simulate pre-TCR function and promote beta-selection. These results suggest that the pre-TCR complex can deliver its signal autonomously through oligomerization of the pre-TCR alpha-chain mediated by charged residues.
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