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Yamasaki S , Ishikawa E , Sakuma M , Ogata K , Sakata-Sogawa K , Hiroshima M , Wiest DL , Tokunaga M , Saito T
Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development
Nature Immunology. 2005 Dec;eFIRST date :5
AbstractThe 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.