The kinetics of hemolytic plaque formation III. inhibition of plaques by antigen

Abstract

Equations are presented which can be used to describe the inhibition of plaques by multifunctional antigen which binds γG antibody bivalently. The interaction is treated as a bimolecular reaction which is irreversible within the time of the experiment. It is shown that under these conditions the characteristics of the inhibition curve, and their relationship to kinetic and thermodynamic parameters are strongly dependent upon how antibody interacts with RBCs. When the epitope coating is dense, multivalent attachment of antibody is likely and the interaction is considered irreversible. When the epitope coating is sparse, only rapid, reversible univalent attachment is considered and local equilibrium is assumed to hold. The first case leads to an abrupt inhibition curve whose position is determined by the forward rate constant and RBC density. The second case leads to broad asymmetric curves. For this situation the relation between the extent of inhibition and the affinity of the population is generally complicated and reliable affinity information is difficult to obtain. This is contrasted to results obtained previously for unifunctional inhibitors from which reliable affinity information can, in principle, be obtained. The results emphasize the need for carefully designed experiments if affinity information is to be obtained from inhibition studies.