Interaction of Interleukin-2 with its Cell Surface Receptors: Interpretation of Equilibrium Binding Experiments via Scatchard Plots

The high affinity receptor for interleukin 2 (IL-2) is composed of at least two chains, a p55 chain that binds IL-2 with low affinity and a p75 chain that binds with intermediate affinity. Two molecular mechanisms have been proposed for the formation of the high affinity receptor-ligand complex. The affinity conversion model proposed by Honjo and coworkers (Saito et al., 1988) suggests that the high affinity receptor is formed via stepwise binding reactions in which IL-2 first binds to the p55 chain and the resulting complex then associates with the p75 chain to form a high affinity ternary complex. In the preformed heterodimer model the p55 and p75 chains form a non-covalently linked high affinity heterodimer in the absence of IL-2. We analyze these models theoretically and show that they can be distinguished on the basis of equilibrium binding experiments using cell lines expressing different numbers of p55 chains. We show that published IL-2 binding studies are consistent with a model in which a large concentration of preformed heterodimers is present on the cell surface and inconsistent with a model in which preformed heterodimers are absent from the cell surface.