Interpretation of biphasic dissociation kinetics for isomeric class II major histocompatibility complex-peptide complexes.

Antigenic peptides bound to class II major histocompatibility complex (MHC) proteins play a key role in the distinction between "self" and "nonself" by the cellular immune system. Although the formation and dissociation of these complexes are often thought of in terms of the simple mechanism [formula in text], studies of MHC-peptide dissociation kinetics suggest that multiple interconverting forms of the bound MHC-peptide complex can be formed. However, the precise relationship between observed dissociation data and proposed multiple-complex mechanisms has not been systematically examined. Here we provide a mathematical analysis to fill this gap and attempt to clarify the kinetic behavior that is expected to result from the proposed mechanisms. We also examine multiple-complex dynamics that can be "hidden" in conventional experiments. Although we focus on MHC-peptide interactions, the analysis provided here is fully general and applies to any ligand-receptor system having two distinct bound states.