Some Physical Chemical Aspects of Receptor-Ligand Interactions

Abstract

Quantitative evaluations of a variety of binding reactions of interest to immunologists have usually assumed that the reactants are homogenously dispersed in solution for purposes of calculation. In fact, many of these reactions involve cell-bound "receptors" which are present at exceedingly high local concentrations on discrete particles. We describe how such a distribution can influence the experimentally measured binding constants. We also briefly consider the additional complexities introduced when multipoint attachment between the ligand and cell-bound receptors is possible, and discuss the possible biological implications.

Anomalous binding of epidermal growth factor to A431 cells is due to the effect of high receptor densities and a saturable endocytic system.

“…Recently, Erickson and his collegues (1987) have provided the first experimental demonstration of the effect of receptor density on ligand binding. They confirm the prediction that the binding of a ligand to a cell will be diffusion controlled when the following relationship is true (DeLisi and Metzger, 1976).…”

Specific cellular stimulation in the primary immune response: a quantized model.

“…As noted above, for an antibody with intrinsic affinity of 1.5 x 104, the functional affinity, K1, would be 1.5 x 104 for a monovalent antibody, 1.5 x 107-108 for a divalent antibody, and .1010 for a multivalent antibody. It has previously been found experimentally (5,16) that (q -1) 10 and Soa-10-11 M. Using these values in Eq. 13 for calculating 's, one obtains the values in the third column of Table 1.…”

“…The first part ofthis paper presents a quantitative description of the immunon model based on elementary physical-chemical considerations similar to those used by others for describing cell surface events (8)(9)(10)(11)(12)(13)(14)(15). In the second part of the paper, this description of the immunon model is used to predict, in a quantitative manner, certain features of the specific immune response.…”

IgE receptors on human basophils. Relationship to serum IgE concentration.

“…We recognize that such estimates of average equilibrium constants as we have derived reflect not only the intrinsic binding constants of the molecular interaction but also the contribution of membrane placement and distribution of the receptors (16,17). The differences in calculated association constants among our donors may be due to one or more of the following: (a) heterogeneity of IgE receptors on human basophils; (b) structural heterogeneity of the Fc portion of IgE; (c) contribution to binding by IgE-bearing lymphocytes or monocytes at high serum IgE levels.…”