Evidence that Structural Rearrangements and/or Flexibility during TCR Binding Can Contribute to T Cell Activation

Michelle Krogsgaard, Nelida Prado, Erin J. Adams, Xiao Lin He, Dar Chone Chow, Darcy B. Wilson, K. Christopher Garcia*, Mark M. Davis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

192 Scopus citations

Abstract

While in many cases the half-life of T cell receptor (TCR) binding to a particular ligand is a good predictor of activation potential, numerous exceptions suggest that other physical parameter(s) must also play a role. Accordingly, we analyzed the thermodynamics of TCR binding to a series of peptide-MHC ligands, three of which are more stimulatory than their stability of binding would predict. Strikingly, we find that during TCR binding these outliers show anomalously large changes in heat capacity, an indicator of conformational change or flexibility in a binding interaction. By combining the values for heat capacity (ΔCp) and the half-life of TCR binding (t 1/2), we find that we can accurately predict the degree of T cell stimulation. Structural analysis shows significant changes in the central TCR contact residue of the peptide-MHC, indicating that structural rearrangements within the TCR-peptide-MHC interface can contribute to T cell activation.

Original languageEnglish (US)
Pages (from-to)1367-1378
Number of pages12
JournalMolecular cell
Volume12
Issue number6
DOIs
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Evidence that Structural Rearrangements and/or Flexibility during TCR Binding Can Contribute to T Cell Activation'. Together they form a unique fingerprint.

Cite this