title: Interaction affinity between cytokine receptor components on the cell surface.
abstract: The anti-common gamma chain (gammac) 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-4Ralpha and gammac receptor chains. Affinities for the binding of IL-4 to Cos-7 cells transfected with huIL-4Ralpha, and to PHA blasts expressing both IL-4Ralpha and gammac, were used to estimate the affinity of the key interaction between gammac and the binary IL-4Ralpha.IL-4 complex on the cell surface. This affinity was defined in terms of the dimensionless ratio [IL-4Ralpha.IL-4.gammac]/[IL-4Ralpha.IL-4], which we designate KR. The results show that on PHA blasts this interaction is relatively weak; KR approximately 9, implying that approximately 10% of the limiting IL-4Ralpha chain remains free of gammac even at saturating concentrations of IL-4. This quantitative treatment establishes KR 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.
authors.affiliation: Biogen, Inc., 14 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: A
authors.initials: A
authors.lastname: Whitty
authors.forename: N
authors.initials: N
authors.lastname: Raskin
authors.forename: D L
authors.initials: DL
authors.lastname: Olson
authors.forename: C W
authors.initials: CW
authors.lastname: Borysenko
authors.forename: C M
authors.initials: CM
authors.lastname: Ambrose
authors.forename: C D
authors.initials: CD
authors.lastname: Benjamin
authors.forename: L C
authors.initials: LC
authors.lastname: Burkly
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology / Q000502:physiology; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D018448:Models, Immunological; D020239:Receptor Cross-Talk; D018121:Receptors, Cytokine / Q000502:physiology*; D019948:Receptors, Interleukin-4 / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018121:Receptors, Cytokine; D019948:Receptors, Interleukin-4; D015847:Interleukin-4