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

Shou Yamasaki, Eri Ishikawa, Machie Sakuma, Koji Ogata, Kumiko Sakata-Sogawa, Michio Hiroshima, David L. Wiest, Makio Tokunaga, Takashi Saito

    Research output: Contribution to journalArticlepeer-review

    108 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)67-75
    Number of pages9
    JournalNature Immunology
    Volume7
    Issue number1
    DOIs
    Publication statusPublished - Jan 1 2006

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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