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Science 310 (5751): 1191-1193

Copyright © 2005 by the American Association for the Advancement of Science

Altered TCR Signaling from Geometrically Repatterned Immunological Synapses

Kaspar D. Mossman,1,2,3 Gabriele Campi,4 Jay T. Groves,1,2,3* Michael L. Dustin4*

Abstract: The immunological synapse is a specialized cell-cell junction that is defined by large-scale spatial patterns of receptors and signaling molecules yet remains largely enigmatic in terms of formation and function. We used supported bilayer membranes and nanometer-scale structures fabricated onto the underlying substrate to impose geometric constraints on immunological synapse formation. Analysis of the resulting alternatively patterned synapses revealed a causal relation between the radial position of T cell receptors (TCRs) and signaling activity, with prolonged signaling from TCR microclusters that had been mechanically trapped in the peripheral regions of the synapse. These results are consistent with a model of the synapse in which spatial translocation of TCRs represents a direct mechanism of signal regulation.

1 Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA.
2 Department of Chemistry, University of California, Berkeley, CA 94720, USA.
3 Physical Biosciences and Materials Sciences Divisions, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
4 Department of Pathology, New York University School of Medicine, and the Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, 540 First Avenue, New York, NY 10016, USA.

* To whom correspondence should be addressed. E-mail: JTGroves{at}lbl.gov (J.T.G.); Dustin{at}saturn.med.nyu.edu (M.L.D.)

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