Skip to main content
eScholarship
Open Access Publications from the University of California

Biophysical mechanism of T-cell receptor triggering in a reconstituted system

  • Author(s): James, JR
  • Vale, RD
  • et al.
Abstract

A T-cell-mediated immune response is initiated by the T-cell receptor (TCR) interacting with peptide-bound major histocompatibility complex (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 non-immune 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. © 2012 Macmillan Publishers Limited.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Main Content
Current View