A TCR BINDS TO ANTAGONIST LIGANDS WITH LOWER AFFINITIES AND FASTER DISSOCIATION RATES THAN TO AGONISTS

T lymphocyte activation is mediated by the interaction of specific TCR with antigenic peptides bound to MHC molecules. Single amino acid sub stitutions 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 t he 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 inhi bition assay, we show that the affinities of three different antagonis t peptide-E(k) complexes are similar to 10-50 times lower than that of the wild-type MCC-E(k) complex for the TCR, largely due to an increas ed off-rate. These results suggest that the biological effects of pept ide antagonists and partial agonists may be largely based on kinetic p arameters.