Delineation of IL-5 domains predicted to engage the IL-5 receptor complex

Richard R. Dickason, Marilyn M. Huston, David P. Huston

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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 β-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 α-chain. Together, these analyses target the A/D helical face of IL-5 as the region involved in receptor engagement.

Original languageEnglish (US)
Pages (from-to)1030-1037
Number of pages8
JournalJournal of Immunology
Volume156
Issue number3
StatePublished - Feb 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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