title: Evidence for multiple sites of interaction between IL-12 and its receptor.
abstract: We have previously described the identification of a protein, now designated IL-12R beta 1, that binds 125I-huIL-12 with a Kd of about 10 nM, corresponding to the low affinity 125I-huIL-12 binding sites seen on PHA-activated human lymphoblasts. Using expression cloning techniques, we have recently identified an additional IL-12-binding protein subunit, IL-12R beta 2, which binds 125I-huIL-12 with a Kd of about 5 nM when expressed alone in COS-7 cells. Coexpression of IL-12R beta 1 and IL-12R beta 2 in COS-7 cells results in formation of two classes of 125 I-huIL-12-binding sites with Kds of about 50 pM and 5 nM. Mouse IL-12 p40 subunit homodimer (mo(p40)2) blocked 125I-huIL-12 binding to human IL-12R beta 1, but did not inhibit binding to human IL-12R beta 2. In contrast, anti-huIL-12 monoclonal antibody 20C2, which does not block 125I-huIL-12 binding to human IL-12R beta 1, completely blocked binding to human IL-12R beta 2. These results demonstrate that two classes of IL-12 inhibitors, one that primarily blocks IL-12/IL-12R beta 1 interaction (e.g., mo(p40)2), and one that primarily blocks IL-12/IL-12R beta 2 interaction (e.g., 20C2), can be identified.
authors.affiliation: Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Presky
authors.forename: L J
authors.initials: LJ
authors.lastname: Minetti
authors.forename: S
authors.initials: S
authors.lastname: Gillessen
authors.forename: U
authors.initials: U
authors.lastname: Gubler
authors.forename: R
authors.initials: R
authors.lastname: Chizzonite
authors.forename: A S
authors.initials: AS
authors.lastname: Stern
authors.forename: M K
authors.initials: MK
authors.lastname: Gately
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D006801:Humans; D018664:Interleukin-12 / Q000737:chemistry*; D051379:Mice; D011485:Protein Binding; D018123:Receptors, Interleukin / Q000737:chemistry*; D053707:Receptors, Interleukin-12; D011994:Recombinant Proteins
chemical_list: D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D011994:Recombinant Proteins; D018664:Interleukin-12