Antagonistic mutant proteins of interleukin-4.

Abstract

Interleukin-4 is a major regulator of the immune system, directing e.g. induction of a TH2 phenotype in T-cells, activation of B-cells and synthesis of IgE type antibodies, which are associated with allergic responses. Site-directed mutagenesis has revealed two sites important for receptor interaction on IL-4: site I mediates binding to the IL-4 receptor alpha subunit, and site II is involved in signal transduction through the receptor complex. Specific mutations in site II produced a series of ligands which bound to the receptor with high affinity, but had little or no agonistic activity and inhibited effects of wild type IL-4. The closely related cytokine IL-13, also a mediator of allergic processes, is antagonized as well. Antagonistic site II mutants of human IL-4 are therefore effective inhibitors with therapeutic potential for IL-4 associated diseases like type I hypersensitivity and asthma.

• Authors: A Duschl, T Müller, W Sebald
• Journal: Behring Institute Mitteilungen (Behring Inst Mitt) Issue 96 Pg. 87-94 (Jun 1995) ISSN: 0301-0457 [Print] Germany
• PMID: 7575356 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antigens, CD
• Macromolecular Substances
• Receptors, Interleukin
• Receptors, Interleukin-4
• Interleukin-4
• Immunoglobulin E

Topics

• Amino Acid Sequence
• Animals
• Antigens, CD (immunology, metabolism)
• Asthma (immunology)
• B-Lymphocytes (immunology)
• Binding Sites
• Humans
• Hypersensitivity (immunology)
• Immunoglobulin E (biosynthesis)
• Interleukin-4 (chemistry, immunology, metabolism)
• Macromolecular Substances
• Models, Molecular
• Molecular Sequence Data
• Mutagenesis, Site-Directed
• Point Mutation
• Protein Structure, Secondary
• Receptors, Interleukin (immunology, metabolism)
• Receptors, Interleukin-4
• Signal Transduction
• T-Lymphocytes (immunology)