Nature Immunology 7, 67 - 75 (2005)
Published online: 4 December 2005; Corrected online: 09 December 2005 | doi:10.1038/ni1290
Mechanistic basis of pre–T cell receptor–mediated autonomous signaling critical for thymocyte developmentSho Yamasaki1, Eri Ishikawa1, Machie Sakuma1, Koji Ogata2, Kumiko Sakata-Sogawa3, Michio Hiroshima3, David L Wiest4, Makio Tokunaga3, 5
& Takashi Saito11
Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan. 2
Centre for Computational Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. 3
Single Molecule Immunoimaging, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan. 4
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. 5
Structural Biology Center, National Institute of Genetics, and Department of Genetics, The Graduate University for Advanced Studies, Shizuoka 411-8540, Japan.
Correspondence should be addressed to Takashi Saito saito@rcai.riken.jp 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  -chain mediated formation of the oligomers in vitro. Alteration of these residues eliminated the ability of the pre-TCR -chain to support pre-TCR signaling in vivo. Dimerization but not raft localization of CD3 was sufficient to simulate pre-TCR function and promote  -selection. These results suggest that the pre-TCR complex can deliver its signal autonomously through oligomerization of the pre-TCR -chain mediated by charged residues.
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