Kinetic discrimination in T-cell activation

Joshua D. Rabinowitz, Craig Beeson, Daniel S. Lyons, Mark M. Davis, Harden M. Mcconnell

Research output: Contribution to journalArticlepeer-review

232 Scopus citations

Abstract

We propose a quantitative model for T-cell activation in which the rate of dissociation of ligand from T-cell receptors determines the agonist and antagonist properties of the ligand. The ligands are molecular complexes between antigenic peptides and proteins of the major histocompatibility complex on the surfaces of antigen-presenting cells. Binding of ligand to receptor triggers a series of biochemical reactions in the T cell. If the ligand dissociates after these reactions are complete, the T cell receives a positive activation signal. However, dissociation of ligand after completion of the first reaction but prior to generation of the final products results in partial T-cell activation, which acts to suppress a positive response. Such a negative signal is brought about by T-cell ligands containing the variants of antigenic peptides referred to as T-cell receptor antagonists. Results of recent experiments with altered peptide ligands compare favorably with T-cell responses predicted by this model.

Original languageEnglish (US)
Pages (from-to)1401-1405
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number4
DOIs
StatePublished - Feb 20 1996

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • T-cell receptor
  • antagonism
  • antigen
  • major histocompatibility complex
  • reaction mechanism

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