title: Cooperative interactions between the interleukin 2 receptor alpha and beta chains alter the interleukin 2-binding affinity of the receptor subunits.
abstract: The interleukin 2 (IL-2) receptor (IL-2R) is a multisubunit receptor that includes three major IL-2 binding subunits, the IL-2R alpha, beta, and gamma chains. We have detected and analyzed cooperative interactions between the IL-2R alpha and beta chains (IL-2R alpha and IL-2R beta, respectively) in COS cells transfected with cDNAs encoding the IL-2R alpha, the IL-2R beta, or both cDNAs. We demonstrated that IL-2 F42A, an analog that fails to bind to the isolated IL-2R alpha subunit and would be predicted by the hierarchical affinity-conversion model to have impaired binding to cells expressing both chains, instead readily binds to the IL-2R alpha/beta heterodimer in COS cells. Furthermore, this binding is abolished by the antibody HIEI that separates the two IL-2R subunits. The monoclonal antibodies anti-Tac and Mik-beta 1 directed at the IL-2-binding sites on IL-2R alpha and IL-2R beta, respectively, block ligand binding to the heterodimer. This binding pattern is inconsistent with the strict hierarchical affinity-conversion model that mandates an initial binding of IL-2 to IL-2R alpha followed by binding of the IL-2/IL-2R alpha complex to IL-2R beta. Instead, our results support an alternative model of preformed complexes of IL-2R beta with other IL-2R subunits. In this alternative model, IL-2R alpha and -beta exist in part as preformed complexes in which the affinity of IL-2R beta for IL-2 is altered by the proximity of IL-2R alpha, through mechanisms that do not require the prior binding of IL-2 to IL-2R alpha.
authors.affiliation: Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: E
authors.initials: E
authors.lastname: Roessler
authors.forename: A
authors.initials: A
authors.lastname: Grant
authors.forename: G
authors.initials: G
authors.lastname: Ju
authors.forename: M
authors.initials: M
authors.lastname: Tsudo
authors.forename: K
authors.initials: K
authors.lastname: Sugamura
authors.forename: T A
authors.initials: TA
authors.lastname: Waldmann
mesh_terms: D002460:Cell Line; D007376:Interleukin-2 / Q000378:metabolism*; D046911:Macromolecular Substances; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D015375:Receptors, Interleukin-2 / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D007376:Interleukin-2; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins