CR1 (CD35) AS A CELLULAR RECEPTOR FOR CIQ

描述：（改编自研究者的摘要）需要补充 用于免疫复合物的正常清除，用于启动体液免疫 对生理剂量抗原的反应，用于抗体亲和力成熟 和同种型转换以及记忆 T 细胞反应的发展。 全部 免疫反应的这些重要因素是由细胞介导的 补体片段的受体。 而 C3b、iC3b 的受体， C3d，g，C4b，C5a和C3a是众所周知的，Clq的受体已被 难以捉摸。 严重的自身免疫性疾病证明了 Clq 的重要性 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（CR1、CD35）、C3b/C4b 受体也发挥作用 作为Clq受体。 因此，免疫粘附受体 CD35 能够 结合已固定任何调理补体的免疫复合物 碎片。 在本申请中，建议鉴定 CD35 上的结合位点 Clq;相反，Clq上结合CD35的位点。 因为CD35是 与 Clr 和 Cls 结构同源，Clr 和 Cls 是 C1 血清的其他成分 与 CD35 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，如甘露糖结合蛋白和表面活性蛋白A， 将被评估为 CD35 的配体。 最后，CD35的生物学作用 作为Clq受体将被研究。 CD35在细胞中的作用 已知由 Clq 触发的反应，例如增强的吞噬作用 单核细胞和中性粒细胞； B 细胞产生的 Ig 增强 确定。 使用 Clq 作为 CD35 的配体信号传导将在 吞噬细胞和B细胞。 CD35 相关蛋白的作用是 检查了。 具体来说，先前描述的可能参与 参与 Clq 结合和 Clq 介导反应的分子将是 通过合作研究确定。 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 C1q 与白细胞上 CD35 相互作用的机制。

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.