Anomalous kinetics in antibody-antigen interactions

The kinetics of hapten binding have been studied for one of a series of 12 anti-dinitrophenyl antibodies (Leahy; et al. Proc. Natl. Acad. Sci. U.S.A. 1988 85, 3661-3665). The kinetic on rate is 100-fold less than the diffusion limited rate. Furthermore, the kinetic on rate shows an anomalous temperature dependence that indicates the presence of two or more conformations of the antibody. Proton NMR spectra of the H3,5 protons of tyrosine residues show a temperature dependence of the conformation of one Tyr residue which is found in the combining site. Computer modeling of the structure of this antibody reveals that a portion of the heavy chain D region forms a loop structure which may be capable of inhibiting the access of the hapten to the combining site. Molecular dynamics calculations indicate that this loop is found in a single conformation at 5 °C, but adopts multiple conformations at 45 °C