Altered TCR signaling from geometrically repatterned immunological synapses |
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Authors: | Mossman Kaspar D Campi Gabriele Groves Jay T Dustin Michael L |
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Institution: | Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA. |
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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. |
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