STRUCTURAL AND BIOLOGICAL PROPERTIES OF IDIOTYPES

独特型的结构和生物学特性

• 批准号: 3132720
• 负责人: ALFRED NISONOFF
• 金额: $ 18.88万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-03-01 至 1990-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3132720
• 关键词: Betaherpesvirinae; X ray crystallography; antiantibody; antiidiotype antibody; antiviral antibody; blocking antibody; gene expression; immunoglobulin E; immunoglobulin genes; immunoglobulin structure; monoclonal antibody; nucleic acid sequence; radioimmunoassay; suid alphaherpesvirus 1

The research objectives are: (1) to obtain more information on the structure of immunoglobulins and on the nature of somatic variations that operate on germline genes. For antibodies of an idiotypic family, attempts will be made to correlate sequences with the 3-D structure of one or more members of the family; (2) to better define and quantify antiidiotypes that express an internal image of the original antigen, and to use the principle for induction of antiviral antibodies; (3) to study sequence variations among IgE antibodies of defined idiotype and to compare the nature and extent of these variations with those occurring in other classes; (4) to initiate studies on the regulation of IgE. Project 1 will be approached through X-ray crystallography, carried out by Dr. R. Poljak on monoclonal antibodies we are supplying, and by determination of amino acid sequences (inferred from mRNA sequences). The sequences of minor idiotypes, that are closely related to but divergent from a major cross-reactive idiotype, should add a dimension to the degree of variation on germline DNA sequences that can be investigated. We will quantify anti-Id expressing an internal image of the antigen in several systems and attempt to induce antiviral antibodies (possibly protective) against pseudorabies virus and cytomegalovirus. IgE monoclonal antibodies that express major and minor idiotypes will be sequenced to ascertain the patterns of variability in this Ig class. Finally, sensitive quantitative techniques for total and idiotype-bearing IgE antiphenylarsonate antibodies will be used to initiate studies of IgE regulation. These studies should add to our knowledge of mechanisms of antibody biosynthesis and regulation. Information on structural variations in antibodies is relevant to our understanding of antibody biosynthesis. Studies on internal images of antigens in certain antiidiotypic antibodies may lead to the use of such antibodies as vaccines or as modulators of physiological processes involving cell surface receptors. Studies of IgE and its regulation are relevant to the control of reactions of immediate hypersensitivity, including allergies.

研究目的是：（1）获得更多关于 免疫球蛋白的结构和体细胞变异的性质 对种系基因进行操作。 对于独特型家族的抗体，尝试 将被用来将序列与一个或多个的 3-D 结构相关联 家庭成员； (2) 更好地定义和量化抗独特型 表达原始抗原的内部图像，并利用原理 用于诱导抗病毒抗体； (3)研究序列变异 确定独特型的 IgE 抗体之间的关系，并比较其性质和 这些差异与其他类别中发生的差异的程度； (4) 至 启动IgE调控的研究。 将着手实施项目1 通过 X 射线晶体学，由 R. Poljak 博士对单克隆 我们提供的抗体，并通过氨基酸序列的测定 （从 mRNA 序列推断）。 次要独特型的序列是 与主要的交叉反应独特型密切相关但又不同， 应该增加种系 DNA 序列变异程度的维度 这是可以调查的。 我们将量化表达内部的反Id 多个系统中抗原的图像并尝试诱导抗病毒 针对伪狂犬病病毒的抗体（可能具有保护性）和 巨细胞病毒。 表达主要和次要 IgE 单克隆抗体 将对独特型进行测序以确定变异模式 这堂Ig课。 最后，总和的敏感定量技术 携带独特型的 IgE 抗苯胂酸抗体将用于启动 IgE 调节的研究。 这些研究应该增加我们对抗体机制的了解 生物合成和调节。 有关结构变异的信息 抗体与我们对抗体生物合成的理解相关。 某些抗独特型抗体中抗原内部图像的研究 可能导致使用此类抗体作为疫苗或作为调节剂 涉及细胞表面受体的生理过程。 IgE的研究 及其调节与立即反应的控制有关 超敏反应，包括过敏。