Interaction affinity between cytokine receptor components on the cell surface

The anti-common gamma chain (gamma(c)) mAb CP.B8 is shown to inhibit interleukin 4 (IL-4)-dependent proliferation of phytohemagglutinin (PHA) activated T cells noncompetitively with respect to cytokine by blocking the IL-4-induced heterodimerization of IL-4R alpha and gamma(c) receptor chains. Affinities for the binding of IL-4 to Cos-7 cells transfected with huIL-4R alpha, and to PHA blasts expressing both IL-4R alpha and gamma(c), were used to estimate the affinity of the key interaction between gamma(c), and the binary IL-4R alpha IL-4 complex on the cell surface. This affinity was defined in terms of the dimensionless ratio [IL-4R alpha.IL-4.gamma(c)]/[IL-4R alpha.IL-4], which,ve designate KR, The results show that on PHA blasts this interaction is relatively weak; K-R approximate to 9, implying that approximate to 10% of the limiting IL-4R alpha chain remains free of gamma(c) even at saturating concentrations of IL-4, This quantitative treatment establishes K-R as a key measure of the coupling between ligand binding and receptor activation, providing a basis for functional distinctions between different receptors that are activated by ligand-induced receptor dimerization.