ANALYSIS OF C3D/EBV RECEPTOR (CR2) LIGAND BINDING SITES

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We are seeking funding to identify and characterize the ligand binding sites on human Complement Receptor 2 (CR2) for C3d,g and the Epstein-Barr virus (EBV) using a peptide based pproach. In preliminary experiments utilizing a recombinant DNA based approach, we have localized these sites to a sub-domain of the receptor. We are extending these recombinant studies to further localize critical domains and amino acids by site-directed mutagenesis, homolog-scanning mutagenesis to move mouse CR2 sequence onto human CR2, and construction of soluble recombinant forms of CR2. We propose herein and are seeking funding to synthesize CR2 derived peptides which will be tested or their ability to inhibit C3d,g and EBV binding. Following initial identification of relevant peptides, we will attempt to synthesize derivatives with enhanced activity. Through this coordinated approach to receptor-ligand interaction analysis, it is anticipated that an extensive understanding of these sites will be obtained. This understanding will allow further experimental and perhaps better clinical approaches to immunotherapy and anti-viral therapy mediated through CR2.