SPECIFIC BINDING PROTEINS FOR HUMAN IMMUNOGLOBULIN G

本提案的重点是开发人IgG亚类特异性 细菌结合蛋白这些蛋白质将有价值 定量特异性IgG亚类，研究亚类对 不同的抗原和免疫方案，确定亚类 在生物样品中的分布和纯化单个人IgG 子类。重组细菌IgG亚类试剂的研制 根据这项建议，将提供一个可靠的替代现有的反- 人IgG亚类单克隆抗体已经显示具有 世界卫生组织最近赞助的研究存在严重局限性， Organization.在I期研究中，重组细菌结合 对人IgG 3特异的蛋白质被证明对 灵敏和特异性检测/定量多种人IgG 3 分析格式。特异性针对每一种抗体的候选结合蛋白。 还鉴定了其它单独的IgG亚类。在第二阶段， 重组IgG 1、IgG 2和IgG 4特异性人IgG亚类结合 蛋白质将被生产和测试用于诊断 免疫化学方法和亲和纯化方法。以及 已建立的基因工程技术将用于产生 具有所需功能的重组亚类结合蛋白 特色II期研究将提供人IgG亚类特异性 用于基础研究、免疫诊断和生物加工的试剂。 拟议的商业应用： 细菌结合蛋白能选择性地结合特定的人 IgG亚类将为研究和诊断提供关键试剂 免疫测定。可以检测IgG亚类的细菌蛋白， 类似于葡萄球菌蛋白A或链球菌蛋白G 也将有重大的商业应用， IgG亚类抗体的纯化。

The focus of this proposal is to develop human IgG subclass specific bacterial binding proteins. These proteins will be of value for quantifying specific IgG subclasses, studying subclass responses to different antigens and immunization protocols, determining subclass distribution in biological samples and purifying individual human IgG subclasses. The recombinant bacterial IgG subclass reagents developed under this proposal will provide a reliable alternative to existing anti- human IgG subclass monoclonal antibodies which have been shown to have serious limitations in recent studies sponsored by the World Health Organization. During Phase I studies, a recombinant bacterial binding protein specific for human IgG3 was shown to be effective for the sensitive and specific detection/quantitation of human IgG3 in a variety of assay formats. Candidate binding proteins specific for each of the other individual IgG subclasses were also identified. In Phase II, recombinant IgG1, 1gG2 and IgG4 specific human IgG subclass binding proteins will be produced and tested for utility in diagnostic immunochemical procedures and affinity purification methods. Well established genetic engineering techniques will be used to generate recombinant subclass binding proteins with the desired functional characteristics. Phase II studies will provide human IgG subclass specific reagents for use in basic research, immunodiagnostics and bioprocessing. Proposed commercial applications: Bacterial binding proteins that could bind selectively to specific human IgG subclasses will provide key reagents for research and diagnostic immunoassays. Bacterial proteins that could detect IgG subclasses in an analogous fashion to staphylococcal protein A or streptococcal protein G would also have significant commercial applications for large scale purification of IgG subclass antibodies.