TAILIEUCHUNG - Báo cáo Y học: Functional epitope of common c chain for interleukin-4 binding

Interleukin 4 (IL-4) can act on target cells through an IL-4 receptor complex consisting of the IL-4 receptorachain and the commoncchain (cc). An IL-4 epitope forccbinding has previously been identi®ed. In this study, thecc residues involved in IL-4 binding were de®ned by alanine-scanning mutational analysis. The epitope comprisescc residues I100, L102, and Y103 on loop EF1 together with L208 on loop FG2 as the major binding determinants. | Eur. J. Biochem. 269 1490-1499 2002 FEBS 2002 Functional epitope of common c chain for interleukin-4 binding Jin-Li Zhang Manfred Buehner and Walter Sebald Theodor-Boveri-Institut fur Biowissenschaften Biozentrum Physiologische Chemie II Universitat Wurzburg Germany Interleukin 4 IL-4 can act on target cells through an IL-4 receptor complex consisting of the IL-4 receptor a chain and the common c chain cc . An IL-4 epitope for cc binding has previously been identified. In this study the cc residues involved in IL-4 binding were defined by alanine-scanning mutational analysis. The epitope comprises cc residues I100 L102 and Y103 on loop EF1 together with L208 on loop FG2 as the major binding determinants. These predominantly hydrophobic determinants interact with the hydrophobic IL-4 epitope composed of residues I11 N15 and Y124. Double-mutant cycle analysis revealed co-operative interaction between cc and IL-4 side chains. Several cc residues involved in IL-4 binding have been previously shown to be mutated in X-linked severe combined immunodefciency. The importance of these binding residues for cc function is discussed. These results provide a basis for elucidating the molecular recognition mechanism in the IL-4 receptor system and a paradigm for other cc-dependent cytokine receptor systems. Keywords common c chain interleukin 4 mutagenesis protein-protein interaction structure function. Interleukin-4 IL-4 is a multifunctional cytokine that plays a critical role in the regulation of immune responses 1 2 . It induces the generation of Th2-dominated early immune response 3 and determines the immunoglobulin class switching to IgE 4 . Dysregulation of IL-4 function is strongly correlated with type I hypersensitivity reactions such as allergies and asthma 5 . The IL-4 receptor complex is therefore a potential target for the development of antiallergic drugs. The central role of IL-4 in the development of Th2 cells suggests that it may be of beneft in the treatment of .

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