Altered TCR signaling from geometrically repatterned immunological synapses.
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.
Mossman
Kaspar D
KD
Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA.
Campi
Gabriele
G
Groves
Jay T
JT
Dustin
Michael L
ML
D020816:Amino Acid Motifs; D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D002478:Cells, Cultured; D008051:Lipid Bilayers; D051379:Mice; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D008051:Lipid Bilayers; D011948:Receptors, Antigen, T-Cell