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Cutting Edge: Effects of an Allergy-Associated Mutation in the Human IL-4R (Q576R) on Human IL-4-Induced Signal Transduction¹

Helen Y. Wang^*, Chris P. Shelburne, Jose Zamorano^*, Ann E. Kelly^*, John J. Ryan and Achsah D. Keegan^2,*

^* Department of Immunology, Jerome Holland Laboratories, American Red Cross, Rockville, MD 20855; and Department of Biology, Virginia Commonwealth University, Richmond, VA 23284

A mutation in the human (hu) IL-4R, Q576R, has been linked with allergy in humans. Increased sensitivity of patients cells with this mutation to IL-4 suggest that a Q576R change enhances IL-4 signaling. To directly test this hypothesis, we analyzed the ability of huIL-4R cDNA bearing the Q576R and Y575F mutations to signal tyrosine phosphorylation, DNA-binding activity, proliferation, protection from apoptosis, and CD23 induction in response to huIL-4 in murine cells. Responses generated by the Q576R and Y575F mutants were similar to those of the wild-type receptor, using various concentrations of huIL-4 and times of stimulation. These results indicate that neither the Q576R nor the Y575F mutations have a significant direct effect on IL-4 signal transduction, and that hypersensitive induction of CD23 in cells derived from human allergy patients may be due to different and/or additional alterations in the IL-4 signaling pathway.

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