IL-4δ2 as an alternative IL-4 form: structure and test system development

Abstract

Epidemiological studies indicate that the prevalence of bronchial asthma in various countries is approximately 10-15%, and that of allergic rhinitis is over 20%. The number of people suffering from allergic diseases nearly doubles every decade, and the detailed reasons for this phenomenon remain unclear. The ability of T cells (CD4+) to recognize allergens and respond with the release of certain cytokines is a key factor in the regulation of IgE synthesis, the activation of mast cells, basophils, and eosinophils, and the generation of inflammation. IgE antibody production depends primarily on the ratio of the cytokines IL-4 and γ-interferon, and inhibition of IL-4 secretion appears to be an effective approach to allergy therapy. A new mechanism for regulating IL-4 activity has recently been described, involving an alternative form of this protein, IL-4δ2. An alternative form of the IL-4δ2 protein is formed as a result of natural alternative splicing of the IL-4 gene. It has been established that IL-4δ2 (recombinant) suppresses the proliferation of T-lymphocytes and also competes with the full-length form of the protein for common receptors on immunocompetent cells. The aim of this study was to analyze the spatial and antigenic structures of the cytokines IL-4 and IL-4δ2, to search for discriminatory monoclonal antibodies for both cytokines, and to develop a system for the quantitative determination of IL-4δ2 in biological samples. An analysis of the antigenic and three-dimensional structures of human cytokines IL-4 and its alternative splicing variant IL-4δ2 was performed. A monoclonal antibody specific for IL-4δ2 was obtained for the first time. The developed test system for the quantitative determination of IL-4δ2 concentration in biological samples can be used in monitoring diseases associated with increased IL-4 secretion.