The cell surface expression level of the human interleukin‐5 receptor α subunit determines the agonistic/antagonistic balance of the human interleukin‐5 E13Q mutein
- 1 February 1999
- journal article
- research article
- Published by Wiley in European Journal of Biochemistry
- Vol. 259 (3) , 954-960
- https://doi.org/10.1046/j.1432-1327.1999.00148.x
Abstract
The human interleukin‐5 (IL‐5) receptor consists of an α‐chain that specifically binds the ligand with intermediate affinity, and a βc‐chain, that associates with the IL‐5/IL‐5Rα complex, leading to a high‐affinity, signal transducing receptor complex. Structure‐function studies showed that modification of the putative βc‐chain binding site in IL‐5 (E13Q mutein) converted the molecule into an antagonist. However, analysis of the effect of this mutant IL‐5 on COS‐1 cells transfected with both receptor subunits, did not show reduced interaction with the βc subunit [Tavernier, J., Tuypens, T., Verhee, A., Plaetinck, G., Devos, R., Van der Heyden, J., Guisez, Y. & Oefner, C. (1995) Proc. Natl Acad. Sci. USA89, 7041–7045]. To gain more insight into the mechanism of IL‐5 antagonism by E13Q, we tested its biological activity on two FDC‐P1 subclones that express clearly different numbers of α‐subunits yet an almost constant number of murine βc‐subunits. Here we show that E13Q has a biological activity comparable to wild‐type IL‐5 only when a high number of α‐chains is present on the cells. Confirming the critical role of the IL5Rα cell‐surface expression level, treatment with suboptimal doses of a neutralising anti‐IL‐5Rα antibody results in reduced activity of the mutant but not of wild‐type IL‐5.Keywords
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