TY - JOUR
T1 - Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development
AU - Yamasaki, Sho
AU - Ishikawa, Eri
AU - Sakuma, Machie
AU - Ogata, Koji
AU - Sakata-Sogawa, Kumiko
AU - Hiroshima, Michio
AU - Wiest, David L.
AU - Tokunaga, Makio
AU - Saito, Takashi
PY - 2006/1
Y1 - 2006/1
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Animals
KW - Cell Differentiation/immunology
KW - Hematopoietic Stem Cells/cytology
KW - Humans
KW - Membrane Glycoproteins/chemistry
KW - Microscopy, Confocal
KW - Molecular Sequence Data
KW - Receptors, Antigen, T-Cell, alpha-beta/chemistry
KW - Signal Transduction/immunology
KW - T-Lymphocytes/cytology
UR - http://www.scopus.com/inward/record.url?scp=29244457799&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000234139700020&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1038/ni1290
DO - 10.1038/ni1290
M3 - Article
C2 - 16327787
SN - 1529-2908
VL - 7
SP - 67
EP - 75
JO - Nature Immunology
JF - Nature Immunology
IS - 1
ER -