CR1 (CD35) AS A CELLULAR RECEPTOR FOR CIQ

CR1 (CD35) 作为 CIQ 的细胞受体

• 批准号: 6373824
• 负责人: ANNE NICHOLSON-WELLER
• 金额: $ 30.32万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6373824
• 关键词: B lymphocyte; CD antigens; antibody formation; binding proteins; biological signal transduction; chemical binding; complement receptor; human subject; immune complex; mannose; monocyte; neutrophil; phagocytosis; receptor binding; surfactant; tissue /cell culture

DESCRIPTION: (Adapted from Investigator's abstract) Complement is required for the normal clearance of immune complexes, for initiation of the humoral response to physiological doses of antigen, for antibody affinity maturation and isotype switching and for development of a memory T cell response. All of these vital elements of the immunologic response are mediated by cellular receptors for complement fragments. While the receptors for C3b, iC3b, C3d,g, C4b, C5a and C3a are well-known, the receptor for Clq has been elusive. The importance of Clq is exemplified by the severe autoimmune diseases caused by Clq deficiency, including glomerulonephritis and vasculitis. In preliminary studies, our laboratories have demonstrated that complement receptor type 1 (CR1, CD35), the C3b/C4b receptor, also functions as a Clq receptor. Thus the immune adherence receptor, CD35, is able to bind immune complexes that have fixed any of the opsonizing complement fragments. In this application, it is proposed to identify the binding site on CD35 for Clq; and conversely, the site on Clq for binding CD35. Because CD35 is structurally homologous to Clr and Cls, the other components of C1, serum and membrane proteins structurally homologous to CD35 will be assessed as potential Clq receptors. Similarly, proteins structurally and functionally related to Clq, such as mannose binding protein and surfactant protein A, will be assessed as ligands for CD35. Finally, the biological role of CD35 as a Clq receptor will be investigated. The role of CD35 in the cellular response known to be triggered by Clq, such as enhanced phagocytosis by monocytes and neutrophils; and enhanced Ig production by B cells will be determined. Using Clq as a ligand signaling by CD35 will be investigated in phagocytes and B cells. A role of CD35 associated proteins will be examined. Specifically, the possible participation of previously described molecules involved in Clq binding and Clq mediated responses will be determined by collaborative studies. When completed, proposed research will clarify the role of Clq in the handling of immune complexes, and address the mechanisms underlying the interaction of C1q with CD35 on leukocytes.

描述：（改编自研究者摘要）需要补充 对于免疫复合物的正常清除，对于体液免疫的启动， 对生理剂量抗原的应答，用于抗体亲和力成熟 和同种型转换以及记忆T细胞应答的发展。 所有 免疫反应的这些重要元素是由细胞介导的， 补体片段的受体。 而C3 b，iC 3b， C3 d、C3 g、C4 b、C5 a和C3 a是众所周知的，C1 q的受体已经被发现。 难以捉摸。 Clq的重要性通过严重的自身免疫性疾病来例证。 由Clq缺乏引起的疾病，包括肾小球肾炎和 血管炎 在初步研究中，我们的实验室已经证明， 补体受体1型（CR 1，CD 35），C3 b/C4 b受体，也起作用 作为Clq受体。 因此，免疫粘附受体CD 35能够 结合免疫复合物，该免疫复合物固定任何调理补体， 片段 在本申请中，提出鉴定CD 35上的结合位点， C1 q上的位点;相反，C1 q上用于结合CD 35的位点。 因为CD 35是 结构上与Clr和Cls同源，Clr和Cls是C1的其他组分，血清 与CD 35结构同源的膜蛋白将被评估为 潜在的Clq受体。 同样，蛋白质在结构和功能上 与Clq相关的蛋白质，如甘露糖结合蛋白和表面活性蛋白A， 将被评估为CD 35的配体。 最后，CD 35的生物学作用 作为Clq受体将被研究。 CD 35在细胞凋亡中的作用 已知由Clq触发的免疫应答，例如由Clq引起的增强的吞噬作用。 单核细胞和中性粒细胞;并且将增强B细胞的IG产生 测定 使用Clq作为通过CD 35的配体信号传导将在下文中研究。 吞噬细胞和B细胞。 CD 35相关蛋白的作用将是 考察 具体而言，先前描述的可能参与 参与Clq结合和Clq介导的反应的分子将被 由合作研究决定。 完成后，拟议的研究将 阐明Clq在处理免疫复合物中的作用，并解决 C1 q与白细胞上的CD 35相互作用的潜在机制。