Fc receptors for IgE (FcR Gamma) have been identified on various cell types, including mast cells, basophils, macrophages and lymphocytes. The receptors on mast cells and basophils are directly involved in the IgE-mediated hypersensitivity reactions. FcR Gamma-bearing lymphocytes are important for the regulation of the IgE antibody response. The objective of this research is to study the gene expression, structure and function of this group of receptors, applying recombinant DNA technology. First, the gene and protein structure of FcR Gamma will be determined. We have already cloned cDNA coding for an FcR Gamma protein found in basophils and the relationship of this protein to previously identified subunits of the basophil FcR Gamma will be established. Genes for other subunits of the basophil FcR Gamma and the gene for the lymphocyte FcR Gamma will be cloned. Structural homology between basophil and lymphocyte FcR Gamma will be determined. Second, the structure-function relationship of FcR Gamma will be established. The subunits of basophil FcR Gamma required for expressing IgE-binding activity on the cell surface and for transmitting signals for the activation of basophils will be determined. This study will be performed by translation in Xenopus oocytes of mRNA coding for FcR Gamma subunits or by transfection of appropriate cells with cloned genes. To establish the function of lymphocyte FcR Gamma, the relationship between the receptor and IgE-binding factors, previously identified to be involved in the regulation of IgE responses and structurally-related to the receptor, will be determined. The cloned lymphocyte FcR Gamma gene will be used for this study. Third, the mechanism of regulation of FcR Gamma gene expression will be elucidated. The cloned genes for basophil or lymphocyte FcR Gamma will be used as probes to study the expression of FcR Gamma in various cell types under various conditions. DNA sequences in the receptor genes controlling the level and possibly the tissue specificity of FcR Gamma gene expression will be identified. It is known that lymphocytes respond to exposure to IgE by an increase in the expression of FcR Gamma. The DNA sequence of the lymphocyte FcR Gamma gene that is involved in such a response will be determined. Results from these studies should advance our understanding of human allergic disorders significantly as well as provide invaluable insights into the mechanisms of regulations and effector functions in the immune system in general.
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