Qualitative and quantitative differences in T cell receptor binding of agonist and antagonist ligands

The kinetics of interaction between TCR and MHC-peptide show a general rela tionship between affinity and the biological response, but the reported kin etic differences between antigenic and antagonistic peptides are very small . Here, we show a remarkable difference in the kinetics of TCR interactions with strong agonist ligands at 37 degrees C compared to 25 degrees C. This difference is not seen with antagonist/positive selecting ligands. The int eraction at 37 degrees C shows biphasic binding kinetics best described by a model of TCR dimerization. The altered kinetics greatly increase the stab ility of complexes with agonist ligands, accounting for the large differenc es in biological response compared to other ligands. Thus, there may be an allosteric, as well as a kinetic, component to the discrimination between a gonists and antagonists.