Efficient T cell activation requires an optimal dwell-time of interaction between the TCR and the pMHC complex

Nat Immunol. 2001 Mar;2(3):229-34. doi: 10.1038/85286.


Cytotoxic T cell (CTL) activation by antigen requires the specific detection of peptide-major histocompatibility class I (pMHC) molecules on the target-cell surface by the T cell receptor (TCR). We examined the effect of mutations in the antigen-binding site of a Kb-restricted TCR on T cell activation, antigen binding and dissociation from antigen.These parameters were also examined for variants derived from a Kd-restricted peptide that was recognized by a CTL clone. Using these two independent systems, we show that T cell activation can be impaired by mutations that either decrease or increase the binding half-life of the TCR-pMHC interaction. Our data indicate that efficient T cell activation occurs within an optimal dwell-time range of TCR-pMHC interaction. This restricted dwell-time range is consistent with the exclusion of either extremely low or high affinity T cells from the expanded population during immune responses.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens / genetics
  • Antigens / immunology
  • Cytokines / biosynthesis
  • Half-Life
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Hybridomas
  • Kinetics
  • Lymphocyte Activation*
  • Mutagenesis, Site-Directed
  • Nucleocapsid / genetics
  • Nucleocapsid / immunology
  • Nucleocapsid Proteins*
  • Peptides / genetics
  • Peptides / immunology*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*


  • Antigens
  • Cytokines
  • Histocompatibility Antigens Class I
  • Nucleocapsid Proteins
  • Peptides
  • Receptors, Antigen, T-Cell