Dependence of T cell antigen recognition on T cell receptor-peptide MHC confinement time

Immunity. 2010 Feb 26;32(2):163-74. doi: 10.1016/j.immuni.2009.11.013. Epub 2010 Feb 4.


T cell receptor (TCR) binding to diverse peptide-major histocompatibility complex (pMHC) ligands results in various degrees of T cell activation. Here we analyze which binding properties of the TCR-pMHC interaction are responsible for this variation in pMHC activation potency. We have analyzed activation of the 1G4 cytotoxic T lymphocyte clone by cognate pMHC variants and performed thorough correlation analysis of T cell activation with 1G4 TCR-pMHC binding properties measured in solution. We found that both the on rate (k(on)) and off rate (k(off)) contribute to activation potency. Based on our results, we propose a model in which rapid TCR rebinding to the same pMHC after chemical dissociation increases the effective half-life or "confinement time" of a TCR-pMHC interaction. This confinement time model clarifies the role of k(on) in T cell activation and reconciles apparently contradictory reports on the role of TCR-pMHC binding kinetics and affinity in T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clone Cells
  • Cytotoxicity, Immunologic
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology
  • HLA-A2 Antigen / metabolism*
  • Humans
  • Interferon-gamma / metabolism
  • Lymphocyte Activation
  • Models, Immunological
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / immunology*
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology*
  • Protein Binding
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Surface Plasmon Resonance
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • T-Lymphocytes, Cytotoxic / pathology
  • Time Factors
  • Transfection


  • HLA-A2 Antigen
  • Neoplasm Proteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • peptide NY-ESO-1 157-165
  • Interferon-gamma