CONSTANT DOMAIN MODULATION OF ANTIBODY ACTIVITY

抗体活性的恒定域调节

• 批准号: 3454705
• 负责人: NEIL S GREENSPAN
• 金额: $ 8.88万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3454705
• 关键词: Streptococcus pneumoniae; acidity /alkalinity; antigen antibody reaction; bacterial antigens; chemical binding; electron microscopy; enzyme linked immunosorbent assay; gene expression; immunoglobulin G; immunoglobulin genes; immunoglobulin structure; laboratory mouse; laboratory rat; monoclonal antibody; protein structure function; radioimmunoassay; radiotracer; temperature

The major objectives of this proposal are to clarify the molecular basis for, and the significance and generality of, Fc region-dependent, cooperative binding of antibodies to antigen. In addition, we will characterize IgG subclass-associated difference in other functional properties. The experimental approaches to be employed are delineated below. First, the functional affinities of IgG antibodies expressing different heavy chain constant domains will be compared with respect to different (particularly with regard to epitope spacing) forms of antigen under a variety of conditions (e.g., temperature or ionic strength). Monoclonal antibodies (mAbs) of different IgG subclasses, but expressing identical, or comparable, variable domains will be used for these studies. Second, the sites in the gamma 3 Fc region that are involved in cooperative binding will be mapped by serologic and electron microscopic methods. Third, the murine IgG subclasses will be compared with respect to clearance and protection in a murine model infection with Streptococcus pneumoniae. Forth, mAbs with novel binding phenotypes will be selected and characterized, and new strategies for endowing antibodies with the ability to bind cooperatively will be evaluated. These studies should contribute to an understanding of the functional differences among IgG subclasses, particularly in the contexts of anti- bacterial and anti-polysaccharide antibody responses. Further more, by increasing our understanding of the relationships between antibody constant domain structure and function, these studies should suggest novel ways to alter antibody structure to enhance desired functional properties.

该提案的主要目标是阐明分子基础 对于FC区域依赖性的重要性和一般性， 抗体与抗原的合作结合。此外，我们将 表征其他功能中IgG亚类相关的差异 特性。划定要使用的实验方法 以下。 首先，IgG抗体的功能亲和力表达不同 重链恒定域将与不同的域进行比较 （特别是关于表位间距） 各种条件（例如温度或离子强度）。单克隆 不同IgG亚类的抗体（mAb），但表达相同的抗体 或可比较的可变域将用于这些研究。 其次，伽马3 fc区域中涉及的地点 合作结合将由血清学和电子显微镜映射 方法。 第三，将比较鼠IgG子类 用链球菌感染鼠模型感染的清除和保护 肺炎。 第四，将选择具有新型结合表型的mAb，并且 特征是赋予抗体的新策略 将评估合作绑定的能力。 这些研究应该有助于理解功能 IgG亚类之间的差异，特别是在反抗 细菌和抗 - 糖类抗体反应。更重要的是 提高我们对抗体之间关系的理解 恒定的域结构和功能，这些研究应表明 改变抗体结构以增强所需功能的新方法 特性。