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Published Online September 25, 2003
Science DOI: 10.1126/science.1086507

Reports

Submitted on May 6, 2003
Accepted on August 26, 2003

The Immunological Synapse Balances T Cell Receptor Signaling and Degradation

Kyeong-Hee Lee 1, Aaron R. Dinner 2, Chun Tu 3, Gabriele Campi 4, Subhadip Raychaudhuri 5, Rajat Varma 4, Tasha N. Sims 4, W. Richard Burack 3, Hui Wu 3, Julia Wang 3, Osami Kanagawa 3, Mary Markiewicz 3, Paul M. Allen 3, Michael L. Dustin 4*, Arup K. Chakraborty 6*, Andrey S. Shaw 3*

1 Department of Pathology and Immunology, Washington University School of Medicine, Box 8118, 660 South Euclid, Saint Louis, MO 63110, USA; Department of Immunology, Genentech, 530 Forbes Boulevard, One DNA Way, South San Francisco, CA 94080, USA.
2 Department of Chemistry, University of California, Berkeley, CA 94720, USA.
3 Department of Pathology and Immunology, Washington University School of Medicine, Box 8118, 660 South Euclid, Saint Louis, MO 63110, USA.
4 Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine and Department of Pathology, New York University, New York, NY 10016, USA.
5 Department of Chemical Engineering, University of California, Berkeley, CA 94720, USA.
6 Department of Chemistry, Department of Chemical Engineering, University of California, Berkeley, CA 94720, USA; Physical Biosciences and Materials Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA.

* To whom correspondence should be addressed. E-mail: shaw{at}pathbox.wustl.edu.

The immunological synapse is a specialized cell-cell junction between T cell and antigen presenting cell (APC) surfaces. It is characterized by a central cluster of antigen receptors, a ring of integrin family adhesion molecules, and temporal stability over hours. The role of this specific organization in signaling for T cell activation has been controversial. We employ in vitro and in silico experiments to determine that the immunological synapse acts as a type of adaptive controller that both boosts T cell receptor (TCR) triggering and attenuates strong signals.


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