Selective inhibition of high- but not low-affinity interleukin 2 binding by lectins and anti-interleukin 2 receptor alpha antibody.
The present study demonstrated that various reagents can specifically reduce the affinity of high-affinity interleukin 2 receptor (IL-2R) but not that of low-affinity IL-2R. They included lectins such as wheat germ agglutinin (WGA), concanavalin A and phytohemagglutinin, and a chemical cross-linker, glutaraldehyde, in addition to anti-IL-2R monoclonal antibodies, HIEI and H-47. The affinity of the high-affinity IL-2R was reduced when the cells were treated with WGA or H-47 before, but not after, addition of 125I-labeled interleukin 2 (IL-2). Their inhibitory effects were also demonstrated by the chemical cross-linking method. On treatment with the reagents, the IL-2 binding to both IL-2R alpha and beta chains was inhibited and these inhibitory effects were seen only when the reagents were added before IL-2 addition, like their high-affinity reducing effects. These results support a supposition that the high affinity IL-2R is generated by assembly of the alpha and beta chains, and suggest that the IL-2 binding to IL-2R alpha and beta chains could induce stable constitution of the high-affinity state of IL-2R, but these affinity modulating reagents could perturb the optimum association between alpha and beta chains to generate the high-affinity IL-2R.
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005976:Glutaral / Q000494:pharmacology; D007376:Interleukin-2 / Q000502:physiology*; D007700:Kinetics; D037102:Lectins / Q000494:pharmacology; D008970:Molecular Weight; D011487:Protein Conformation; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014909:Wheat Germ Agglutinins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D007376:Interleukin-2; D037102:Lectins; D015375:Receptors, Interleukin-2; D014909:Wheat Germ Agglutinins; D005976:Glutaral