On the kinetics of peptide binding to MHC proteins

Abstract

An experimental study of kinetics of peptide binding to MHC proteins [S. Witt, H. McConnell, Acc. Chem. Res. 26 (1993) 442 (and references therein)] showed an unusual phenomenon of the so-called `negative' t 1/2 plots (where t 1/2 is half time of reaching equilibrium concentration of peptide–protein complexes), which is the shorter t 1/2 at lower added peptide concentrations. The bell-shaped curve for t 1/2 as a function of peptide concentration is a seemingly peculiar effect, because in general, binding reactions go faster with an increase of reagent concentrations. It is shown that the suggested explanation of this phenomenon [S. Witt, H. McConnell, Acc. Chem. Res. 26 (1993) 442 (and references therein)] is misleading (and the numerical simulation used to support this explanation is inconsistent with the experimental data), so that the existence of `negative' t 1/2 is in no way to be considered as an experimental indication of the two-step reaction of peptide binding to protein. This article gives a consistent explanation of the bell-shaped t 1/2 plots for peptide–protein association and obtains the criteria for its existence, based exclusively on the formal chemical kinetics analysis of the accepted peptide–protein binding model and briefly discusses the experimental data, which really confirm the existence of the two-step mechanism of binding. The analysis of the maximum location of the half-time curves indicates a controversy between the prediction of the two-step binding model and the experimental data [S. Witt, H. McConnell, Acc. Chem. Res. 26 (1993) 442 (and references therein)]: either more complicated mechanism is involved in peptide–MHC binding or experimental data [S. Witt, H. McConnell, Acc. Chem. Res. 26 (1993) 442 (and references therein)] are not quite accurate.