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Biophysical mechanism of T-cell receptor triggering in a reconstituted system
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James, John R. and Vale, Ronald D. (2012) Biophysical mechanism of T-cell receptor triggering in a reconstituted system. Nature, 487 (7405). pp. 64-69. doi:10.1038/nature11220
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Official URL: http://dx.doi.org/10.1038/nature11220
Abstract
A T cell-mediated immune response is initiated by the T cell receptor (TCR) interacting with peptide-bound MHC (pMHC) on an infected cell. The mechanism by which this interaction triggers intracellular phosphorylation of the TCR, which lacks a kinase domain, remains poorly understood. Here, we have introduced the TCR and associated signalling molecules into a nonimmune cell and reconstituted ligand-specific signalling when these cells are conjugated with antigen presenting cells. We show that signalling requires the differential segregation of a phosphatase and kinase in the plasma membrane. An artificial, chemically-controlled receptor system generates the same effect as TCR-pMHC, demonstrating that the binding energy of an extracellular protein-protein interaction can drive the spatial segregation of membrane proteins without a transmembrane conformational change. This general mechanism may extend to other receptors that rely on extrinsic kinases, including, as we demonstrate, chimaeric antigen receptors being developed for cancer immunotherapy.
| Item Type: | Journal Article | ||||||||
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Medicine > Warwick Medical School |
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| Journal or Publication Title: | Nature | ||||||||
| Publisher: | Nature Publishing | ||||||||
| ISSN: | 0028-0836 | ||||||||
| Official Date: | 5 July 2012 | ||||||||
| Dates: |
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| Volume: | 487 | ||||||||
| Number: | 7405 | ||||||||
| Page Range: | pp. 64-69 | ||||||||
| DOI: | 10.1038/nature11220 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access |
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