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Science 302 (5648): 1218-1222

Copyright © 2003 by the American Association for the Advancement of Science

The Immunological Synapse Balances T Cell Receptor Signaling and Degradation

Kyeong-Hee Lee,1,2* Aaron R. Dinner,3*{ddagger} Chun Tu,1 Gabriele Campi,5 Subhadip Raychaudhuri,4 Rajat Varma,5 Tasha N. Sims,5 W. Richard Burack,1 Hui Wu,1 Julia Wang,1 Osami Kanagawa,1 Mary Markiewicz,1 Paul M. Allen,1 Michael L. Dustin,5{dagger} Arup K. Chakraborty,3,4,6{dagger} Andrey S. Shaw1{dagger}

Abstract: The immunological synapse is a specialized cell-cell junction between T cell and antigen-presenting cell 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 use 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 triggering and attenuates strong signals.

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

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* These authors contributed equally to this work.

{ddagger} Present address: Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.

{dagger} To whom correspondence should be addressed: E-mail: shaw{at} (A.S.S.), arup{at} (A.K.C.), and dustin{at} (M.L.D.)

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CD2-associated Protein (CD2AP) Expression in Podocytes Rescues Lethality of CD2AP Deficiency.
J. A. Grunkemeyer, C. Kwoh, T. B. Huber, and A. S. Shaw (2005)
J. Biol. Chem. 280, 29677-29681
   Abstract »    Full Text »    PDF »
Early Phosphorylation Kinetics of Proteins Involved in Proximal TCR-Mediated Signaling Pathways.
J. C. D. Houtman, R. A. Houghtling, M. Barda-Saad, Y. Toda, and L. E. Samelson (2005)
J. Immunol. 175, 2449-2458
   Abstract »    Full Text »    PDF »
A Theoretical Framework for Quantitative Analysis of the Molecular Basis of Costimulation.
A. Jansson, E. Barnes, P. Klenerman, M. Harlen, P. Sorensen, S. J. Davis, and P. Nilsson (2005)
J. Immunol. 175, 1575-1585
   Abstract »    Full Text »    PDF »
The c-SMAC: sorting it all out (or in).
J. Lin, M. J. Miller, and A. S. Shaw (2005)
J. Cell Biol. 170, 177-182
   Abstract »    Full Text »    PDF »
Ligand-induced conformational change in the T-cell receptor associated with productive immune synapses.
R. M. Risueno, D. Gil, E. Fernandez, F. Sanchez-Madrid, and B. Alarcon (2005)
Blood 106, 601-608
   Abstract »    Full Text »    PDF »
An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R.
E.-K. Jo, H. Wang, and C. E. Rudd (2005)
J. Exp. Med. 201, 1733-1739
   Abstract »    Full Text »    PDF »

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