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Interleukin-2 carbohydrate recognition modulates CTLL-2 cell proliferation.

K Fukushima·K Yamashita
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Abstract

Interleukin-2 (IL-2) specifically recognizes high-mannose type glycans with five or six mannosyl residues. To determine whether the carbohydrate recognition activity of IL-2 contributes to its physiological activity, the inhibitory effects of high-mannose type glycans on IL-2-dependent CTLL-2 cell proliferation were investigated. Man(5)GlcNAc(2)Asn added to CTLL-2 cell cultures inhibited not only phosphorylation of tyrosine kinases but also IL-2-dependent cell proliferation. We found that a complex of IL-2, IL-2 receptor alpha, beta, gamma subunits, and tyrosine kinases was formed in rhIL-2-stimulated CTLL-2 cells. Among the components of this complex, only the IL-2 receptor alpha subunit was stained with Galanthus nivalis agglutinin which specifically recognizes high-mannose type glycans. This staining was diminished after digestion of the glycans with endo-beta-N-acetylglucosaminidase H or D, suggesting that at least a N-glycan containing Man(5)GlcNAc(2) is linked to the extracellular portion of the IL-2 receptor alpha subunit. Our findings indicate that IL-2 binds the IL-2 receptor alpha subunit through Man(5)GlcNAc(2) and a specific peptide sequence on the surface of CTLL-2 cells. When IL-2 binds to the IL-2Ralpha subunit, this may trigger formation of the high affinity complex of IL-2-IL-2Ralpha, -beta, and -gamma subunits, leading to cellular signaling.

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AnimalsCarbohydrate MetabolismCell DivisionDose-Response Relationship, DrugGalanthusHumansInterleukin-2Janus Kinase 1Janus Kinase 3Lymphocyte Specific Protein Tyrosine Kinase p56(lck)MannoseMannosyl-Glycoprotein Endo-beta-N-AcetylglucosaminidaseMiceModels, BiologicalPhosphorylationPolysaccharidesPrecipitin TestsProtein-Tyrosine KinasesReceptors, Interleukin-2Recombinant ProteinsSignal TransductionT-Lymphocytessrc-Family KinasesJournal Article

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K Fukushima, K Yamashita. 2000-11-13. Interleukin-2 carbohydrate recognition modulates CTLL-2 cell proliferation.. https://doi.org/10.1074/jbc.m008781200

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