C1q binding to antibody-coated cells: Predictions from a simple multivalent binding model

Abstract

We have derived a simple mathematical model describing the multivalent binding of Clq to IgG antibody-coated target cells. The model contains the assumptions that the Clq is hexavalent for IgG, that the cell-bound antibody is mobile in the plane of the plasma membrane, and that the six Clq subunits bind sequentially to the cell-surface antibody. We have calculated how Clq would bind at equilibrium to cells coated with different amounts of antibody, and how free monomeric IgG would inhibit this interaction. The model predicts that the degree of binding of Clq to the cells will be strongly enhanced by increasing the cell surface antibody density, but that even small amounts of cell-bound antibody will render the target cells capable of binding Clq. Scatchard plots of Clq binding invariably show negative curvature due to a fall in the density of free antibody sites as the cell-bound antibody becomes saturated with Clq. Over a wide range of cell-bound antibody densities little of the cell-associated Clq is bound pentavalently or hexavalently. While Clq binding is easily inhibitable by free IgG at low levels of cell-bound antibody, this inhibition is progressively overcome by increasing the density of antibody on the cell. This reflects the inherent property of multivalent ligands such as Clq to seek out regions of high site density.