CR1 (CD35) AS A CELLULAR RECEPTOR FOR CIQ

描述：(改编自《调查员摘要》)需要补充 为了免疫复合体的正常清除，为了启动体液 对生理剂量的抗原的反应，以促进抗体亲和力成熟 和同型转换以及记忆性T细胞反应的发展。全 在免疫反应的这些重要元素中，有许多是由细胞 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的受体已经被 难以捉摸。严重的自身免疫反应证明了慢性粒细胞白血病的重要性。 由Clq缺乏引起的疾病，包括肾小球肾炎和 脉管炎。在初步研究中，我们的实验室已经证明 补体受体1型(CR1，CD35)，即C3b/C4b受体，也起作用 作为一种Clq受体。因此，免疫黏附受体CD35能够 结合固定了任何调理补体的免疫复合体 碎片。 在本申请中，建议确定CD35上的结合位点 Clq；反之，Clq上用于结合CD35的位置。因为CD35是 在结构上与Clr和ClS同源，C1的其他成分，血清 在结构上与CD35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也是如此 与Clq相关的蛋白，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 作为一种Clq受体将被研究。CD35在细胞内的作用 已知由Clq触发的反应，如通过 单核细胞和中性粒细胞；以及增强B细胞产生Ig将是 下定决心。使用Clq作为配体通过CD35传递信号将在 吞噬细胞和B细胞。CD35相关蛋白的作用将是 检查过了。具体地说，前面描述的可能的参与 参与Clq结合和Clq介导的反应的分子将是 是由合作研究决定的。完成后，拟议的研究将 阐明Clq在处理免疫复合体中的作用，并解决 C1q与白细胞表面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.