Molecular biology of interleukin-12 receptors.
IL-12 receptors are expressed primarily on activated T and NK cells. Using labeled IL-12, three classes of IL-12-binding sites have been identified on human PHA-activated lymphoblasts. Their Kd values are 5-20 pM (high affinity), 50-200 pM (intermediate affinity), and 2-6 nM (low affinity). Using a monoclonal antibody, a cDNA encoding a human IL-12 receptor was isolated by expression cloning. The homologous mouse cDNA was isolated by cross hybridization. These proteins are gp130-like members of the cytokine receptor superfamily. Individually, however they bind IL-12 with low affinity. An expression cloning approach was undertaken to isolate an additional human IL-12 receptor component that would act as a high-affinity converter. A cDNA encoding another IL-12 receptor was isolated. The mouse homologue was obtained by cross hybridization. These IL-12 receptors are also gp130-like cytokine receptor superfamily members. Because these two types of IL-12 receptors have the general makeup of beta-type cytokine receptor subunits, they are designated as IL-12R beta 1 and IL-12R beta 2. Coexpression of IL-12R beta 1 and IL-12R beta 2 leads to the formation of high-affinity IL-12-binding sites and reconstitution of IL-12-dependent signaling.
Gubler
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Department of Inflammation/Autoimmune Diseases Hoffmann-La Roche Inc., Nutley, New Jersey 07110, USA.
Presky
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DH
D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology; D051379:Mice; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000235:genetics; D053707:Receptors, Interleukin-12; D013601:T-Lymphocytes / Q000502:physiology
D018076:DNA, Complementary; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12