Glycosylation of the interleukin-1 receptor type I is required for optimal binding of interleukin-1.
The two types of cell surface receptors for interleukin-1 (IL-1) are glycoproteins that contain N-glycosidic chains on their extracellular portions. To determine the role of glycosylation of the IL-1 receptor type I (IL-1RtI) in the binding and function of IL-1, we used four plant lectins and glycosidase treatment on two different T-cell lines (EL4-6.1 and D10S) and expressing high number of binding sites for IL-1. The lectins wheat germ agglutinin, phytohemagglutinin, and concanavalin A inhibited in a dose-response manner the IL-1-induced proliferation of D10S cells. Binding of IL-1 was blocked and radioactive IL-1 was displaced from these cells by these lectins. Specific sugars (GlcNAc, NeuAc, Gal-GlcNAc-Man, Man, or alpha-MeMan) did not themselves affect IL-1 binding but reversed the blocking effects of the lectins. The two cell lines differed in their responses to the lectin-mediated inhibition of IL-1 binding. Digestion by N-glycosidase significantly decreased the capacity of cells to bind IL-1, and reduced by approximately 20,000 D the M(r) of the IL-1RtI. Neuraminidase and O-glycanase treatment did not alter the binding of IL-1 to D10S or EL4-6.1 cells. This study demonstrates that glycosylation of the extracellular domain of the IL-1RtI is due to N-linked carbohydrates, that the degree of glycosylation can vary in cells of different lineage, and that this N-linked glycosylation appears to be essential for optimal binding and activity of IL-1 to its type I receptor.
Mancilla
J
J
Department of Medicine, Tufts University School of Medicine, Boston, MA 02111.
Ikejima
T
T
Dinarello
C A
CA
D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D002236:Carbohydrate Conformation; D002460:Cell Line; D006031:Glycosylation; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D037102:Lectins; D051379:Mice; D011485:Protein Binding; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D037102:Lectins; D017472:Receptors, Interleukin-1