Affordable Access

Publisher Website

A TCR Binds to Antagonist Ligands with Lower Affinities and Faster Dissociation Rates Than to Agonists

Authors
Journal
Immunity
1074-7613
Publisher
Elsevier
Publication Date
Volume
5
Issue
1
Identifiers
DOI: 10.1016/s1074-7613(00)80309-x
Disciplines
  • Biology

Abstract

Abstract T lymphocyte activation is mediated by the interaction of specific TCR with antigenic peptides bound to MHC molecules. Single amino acid substitutions are often capable of changing the effect of a peptide from stimulatory to antagonistic. Using surface plasmon resonance, we have analyzed the interaction between a complex consisting of variants of the MCC peptide bound to a mouse class II MHC (E k) and a specific TCR. Using both an improved direct binding method as well as a novel inhibition assay, we show that the affinities of three different antagonist peptide–E k complexes are ∼10–50 times lower than that of the wild-type MCC–E k complex for the TCR, largely due to an increased off-rate. These results suggest that the biological effects of peptide antagonists and partial agonists may be largely based on kinetic parameters.

There are no comments yet on this publication. Be the first to share your thoughts.