CONSTANT DOMAIN MODULATION OF ANTIBODY ACTIVITY

抗体活性的恒定域调节

• 批准号: 3454709
• 负责人: NEIL S GREENSPAN
• 金额: $ 10.89万
• 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 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3454709
• 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 Fc 区域依赖的意义和普遍性， 抗体与抗原的协同结合。此外，我们将 表征 IgG 亚类相关的其他功能差异 特性。描述了要采用的实验方法 以下。 一、表达不同IgG抗体的功能亲和力 重链恒定结构域将与不同的重链恒定结构域进行比较 （特别是关于表位间距）抗原的形式 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， 或类似的可变域将用于这些研究。 其次，γ 3 Fc 区域中涉及的位点 协同结合将通过血清学和电子显微镜进行绘制 方法。 第三，将比较鼠 IgG 亚类 链球菌感染小鼠模型中的清除和保护 肺炎杆菌。 第四，将选择具有新颖结合表型的单克隆抗体并 特征和赋予抗体的新策略 将评估合作结合的能力。 这些研究应该有助于理解功能 IgG 亚类之间的差异，特别是在抗 细菌和抗多糖抗体反应。更进一步，通过 增加我们对抗体之间关系的理解 恒定的结构域结构和功能，这些研究应该表明 改变抗体结构以增强所需功能的新方法 特性。