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Altered TCR Signaling from Geometrically Repatterned Immunological Synapses

Science, 18 November 2005
Vol. 310, Issue 5751, p. 1191-1193
DOI: 10.1126/science.1119238

Altered TCR Signaling from Geometrically Repatterned Immunological Synapses

  1. Kaspar D. Mossman1,2,3,
  2. Gabriele Campi4,
  3. Jay T. Groves1,2,3,*,
  4. Michael L. Dustin4,*
  1. 1 Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA.
  2. 2 Department of Chemistry, University of California, Berkeley, CA 94720, USA.
  3. 3 Physical Biosciences and Materials Sciences Divisions, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  4. 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.
  1. * To whom correspondence should be addressed. E-mail: JTGroves{at}lbl.gov (J.T.G.); Dustin{at}saturn.med.nyu.edu (M.L.D.)

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.

  • Received for publication 23 August 2005.
  • Accepted for publication 24 October 2005.

Citation:

K. D. Mossman, G. Campi, J. T. Groves, and M. L. Dustin, Altered TCR Signaling from Geometrically Repatterned Immunological Synapses. Science 310, 1191-1193 (2005).

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