gC399tr an inhibitor of autoimmunity

描述（由申请人提供）：Emanual Maverakis，M.D.是一位细胞免疫学家，接受过皮肤病学的临床培训。该提案的一个目标是为他提供一段时间的分子生物学和生物化学的指导下的指导培训。Yoshikazu Takada博士是一位生物化学专家，以识别和表征几种整合素而闻名。Maverakis博士的最终目标是发展成为一名独立的医生科学家。为了帮助这种转变，他将学习分子生物学和生物化学，同时表征纤维蛋白原片段的能力，？C399tr，抑制自身免疫。具体的假设是什么？C399tr将能够通过其结合整联蛋白的能力来抑制自身免疫。这一假设基于以下观察。首先，一个良好的特点MAC-1结合位点内存在？C399tr.（MAC-1是巨噬细胞和小胶质细胞表面上的整合素）。第二，对接模拟研究已经确定整合素aV <$3和a4 <$1作为潜在的目标？C399tr.第三，已知针对α 4 β 1整联蛋白的抗体可以预防动物和人类的自身免疫。 以下是该提案的具体目标。 具体目标1：确定整合素和细胞结合？C399tr. 具体目标2：识别？C399tr对免疫反应的影响。 具体目标3：确定是否？C399tr能够抑制自身免疫。

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.