Delineation of IL-5 domains predicted to engage the IL-5 receptor complex.
IL-5 is an interdigitating homodimeric glycoprotein and a member of the helical bundle family of cytokines. IL-5 is a potent activator of eosinophils and a specific promoter of their differentiation. This activity has implicated IL-5 in the pathogenesis of asthma and allergic disease. A detailed understanding of IL-5 structure and function is required to develop immunomodulators of IL-5-mediated inflammatory responses. We generated a panel of neutralizing anti-IL-5 mAbs which were used to map functional domains on IL-5. In addition, the nucleotide sequences for human IL-5, murine IL-5, rat IL-5, and eight human/murine IL-5 chimeras were engineered and expressed in COS-7 cells. These recombinant cytokines and mAbs were used in TF-1 bioassays to identify five functional epitopes on the tertiary structure of IL-5. Residues responsible for the species-specific activity of human IL-5 were identified with the murine BCL1 bioassay. One set of epitopes cluster around the helix A-loop 2 region, which is predicted to engage the IL-5 receptor beta-chain. The second set of epitopes as well as the species specificity domain cluster around the loop 3-helix D region, which is predicted to engage the IL-5 receptor alpha-chain. Together, these analyses target the A/D helical face of IL-5 as the region involved in receptor engagement.
Dickason
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Department of Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Huston
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MM
Huston
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DP
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D003198:Computer Simulation; D018604:Epitope Mapping; D005822:Genetic Vectors; D006801:Humans; D015848:Interleukin-5 / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000276:immunology; D053649:Receptors, Interleukin-5; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5