gC399tr an inhibitor of autoimmunity

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DESCRIPTION (provided by applicant): Emanual Maverakis, M.D. is a cellular immunologist with clinical training in dermatology. One objective of this proposal is to provide him with a period of mentored training in molecular biology and biochemistry under the guidance of Dr. Yoshikazu Takada, an expert biochemist known best for identifying and characterizing several of the ¿1 integrins. Dr. Maverakis' ultimate goal is to develop into an independent physician scientist. To help with this transition, he will learn molecular biology and biochemistry while characterizing the ability of a fragment of fibrinogen, ?C399tr, to inhibit autoimmunity. The specific hypothesis is that ?C399tr will be able to inhibit autoimmunity through its ability to bind integrins. That hypothesis is based on the following observations. First, a well-characterized MAC-1 binding site exists within ?C399tr. (MAC-1 is an integrin on the surface of macrophages and microglia). Second, docking simulation studies have identified integrins aV¿3 and a4¿1 as potential targets for ?C399tr. Third, antibodies directed against a4¿1 integrin are known to prevent autoimmunity in animals and humans. The following are the proposal's specific aims. Specific Aim 1: Identify the integrins and cells bound by ?C399tr. Specific Aim 2: Identify ?C399tr's effect on the immune response. Specific Aim 3: Determine if ?C399tr is able to inhibit autoimmunity.