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Science 295 (5559): 1539-1542

Copyright © 2002 by the American Association for the Advancement of Science

T Cell Receptor Signaling Precedes Immunological Synapse Formation

Kyeong-Hee Lee,1 Amy D. Holdorf,1 Michael L. Dustin,2 Andrew C. Chan,3 Paul M. Allen,1 Andrey S. Shaw1*

The area of contact between a T cell and an antigen-presenting cell (APC) is known as the immunological synapse. Although its exact function is unknown, one model suggests that it allows for T cell receptor (TCR) clustering and for sustained signaling in T cells for many hours. Here we demonstrate that TCR-mediated tyrosine kinase signaling in naïve T cells occurred primarily at the periphery of the synapse and was largely abated before mature immunological synapses had formed. These data suggest that many hours of TCR signaling are not required for T cell activation. These observations challenge current ideas about the role of immunological synapses in T cell activation.

1 Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, Box 8118, Saint Louis, MO 63110, USA.
2 Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University, 540 First Avenue, New York, NY 10016, USA.
3 Genentech, Department of Immunology, 530 Forbes Boulevard, One DNA Way, South San Francisco, CA 94080, USA.
*   To whom correspondence should be addressed. E-mail: shaw{at}

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ADAP-SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell-APC Conjugation.
H. Wang, F. E. McCann, J. D. Gordan, X. Wu, M. Raab, T. H. Malik, D. M. Davis, and C. E. Rudd (2004)
J. Exp. Med. 200, 1063-1074
   Abstract »    Full Text »    PDF »
Imaging the Single Cell Dynamics of CD4+ T Cell Activation by Dendritic Cells in Lymph Nodes.
M. J. Miller, O. Safrina, I. Parker, and M. D. Cahalan (2004)
J. Exp. Med. 200, 847-856
   Abstract »    Full Text »    PDF »
CD26 up-regulates expression of CD86 on antigen-presenting cells by means of caveolin-1.
K. Ohnuma, T. Yamochi, M. Uchiyama, K. Nishibashi, N. Yoshikawa, N. Shimizu, S. Iwata, H. Tanaka, N. H. Dang, and C. Morimoto (2004)
PNAS 101, 14186-14191
   Abstract »    Full Text »    PDF »
Visualization of plasma membrane compartmentalization with patterned lipid bilayers.
M. Wu, D. Holowka, H. G. Craighead, and B. Baird (2004)
PNAS 101, 13798-13803
   Abstract »    Full Text »    PDF »
Immunological Synapse Formation Licenses CD40-CD40L Accumulations at T-APC Contact Sites.
J. Boisvert, S. Edmondson, and M. F. Krummel (2004)
J. Immunol. 173, 3647-3652
   Abstract »    Full Text »    PDF »
Inhibition of T Cell Receptor Signal Transduction by Tyrosine Kinase-interacting Protein of Herpesvirus saimiri.
N.-H. Cho, P. Feng, S.-H. Lee, B.-S. Lee, X. Liang, H. Chang, and J. U. Jung (2004)
J. Exp. Med. 200, 681-687
   Abstract »    Full Text »    PDF »

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