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Updated: Aug 10, 2026

Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay
19:05

Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay

Published on: October 30, 2015

A conformation- and avidity-based proofreading mechanism for the TCR-CD3 complex

Wolfgang W A Schamel1, Ruth M Risueño, Susana Minguet

  • 1Max Planck-Institut für Immunbiologie and University of Freiburg, Stübeweg 51, 79108 Freiburg, Germany.

Trends in Immunology
|March 11, 2006
PubMed

During antigen recognition, T cells show high sensitivity and specificity, and a wide dynamic range. Paradoxically, these characteristics are based on low-affinity receptor-ligand interactions [between the T-cell antigen receptor (TCR-CD3) complex and the antigen peptide bound to MHC]. Recent evidence indicates that the TCR-CD3 is expressed as multivalent complexes in the membrane of non-stimulated T cells and that conformational changes in the TCR-CD3 can be induced by strong but not weak agonists. Here, we propose a thermodynamic model whereby the specificity of the TCR-CD3-pMHC interaction is explained by its multivalent nature. We also propose that the free energy barriers involved in the change in conformation of the receptor impose a response threshold and determine the kinetic properties of recognition. Finally, we suggest that multivalent TCR-CD3s can amplify signals by spreading them from pMHC-engaged TCR-CD3s to unengaged complexes as a consequence of the cooperativity in the system.

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