ANTIGENICITY OF GLOBULAR PROTEINS

球状蛋白的抗原性

• 批准号: 3480643
• 负责人: EMANUEL MARGOLIASH
• 金额: $ 15.7万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 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 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3480643
• 关键词: B lymphocyte; T lymphocyte; antibody receptor; antibody specificity; binding proteins; cell differentiation; clone cells; cytochrome c; globulins; hybridomas; leukocyte activation /transformation; pigeons; surface antigens

To gain a better understanding of the antibody response to a T cell dependent globular protein antigen, a range of T cell hybridomas and B cell hybridomas have been developed that react to the well-studied major antigenic determinant of pigeon cytochrome c. Following the demonstration that T cells respond only to peptide fragments of the protein and that all naive B cells, regardless of their specificity, can be stimulated to antibody synthesis by soluble factors produced by activated T cells, the biology of this system can now be described at the molecular level. Cytochrome c is a particularly effective choice as an antigen, since the chemistry of the protein is well known and it is possible to obtain material of any desired primary structure with the needed radioactive, fluorescent and photoaffinity labels. With such ligands it is intended to study quantitatively the binding of T cell antigenic peptides and cell surface Class II molecules to T cells, resulting in their activation. Similarly, the synergistic bindings of B cell growth and differentiation factors, produced by activated T cells, and of B cell antigen (the intact native protein), to B cells, causing them to proliferate and mature to antibody secreting cells, will be examined quantitatively. The mechanisms by which the cells of the immune system interact by binding to their physiological external ligands, being thereby activated to produce the set of growth factors which will enable the next cell type in the system to be activated by its external ligands to growth and differentiation in a controlled fashion, present an excellent and readily analyzable model for the relation of growth factors to cell growth in general, and of the disturbances that may occur in that relation. The recent demonstration tha the putative transforming proteins of oncogenic viruses are structurally related to growth factors or to their cell surface receptors, provides several possible mechanisms whereby tumorigene is may result from a change in the normal physiological relation of growth factors and their specific cellular receptors. For example, whether certain lymphoid tumors, such as B cell leukemias, result from the production of abberant growth factors or from receptors that have lost normal control sequences, or from receptors that bind and react to the B cell growth factor but can no longer bind or react to the B cell differentiation factor, will be straightforward to determine once the modalities of binding of lymphocytes of the immune system to their physilogical ligands will have been analyzed, as proposed in this study.

为了更好地了解T细胞的抗体反应 依赖球蛋白抗原、一系列T细胞杂交瘤和B细胞 杂交瘤已经被开发出来，可以对研究充分的主要药物产生反应。 鸽子细胞色素c的抗原决定簇 T细胞只对蛋白质的多肽片段有反应，而且所有 幼稚的B细胞，无论其特异性如何，都可以被刺激成 由活化的T细胞产生的可溶性因子合成抗体， 这个系统的生物学现在可以在分子水平上描述。 细胞色素c是一种特别有效的抗原选择，因为 蛋白质的化学成分是众所周知的，有可能获得 具有所需放射性的任何所需初级结构的材料， 荧光和亲光性标签。有了这样的配体，它的目的是 T细胞抗原肽与细胞结合的定量研究 表面II类分子转化为T细胞，导致其活化。 同样，B细胞生长和分化的协同结合 由活化的T细胞产生的因子和B细胞抗原(完整的 天然蛋白)，导致B细胞增殖和成熟到 抗体分泌细胞，将进行定量检测。其作用机制 免疫系统的细胞通过与其结合而相互作用 生理性外部配体，从而被激活以产生SET 这将使系统中的下一种细胞类型成为 被其外部配体激活以促进细胞的生长和分化 受控时尚，提供了一个出色的、易于分析的模型 生长因子与细胞生长的关系，以及与细胞生长的关系 在这种关系中可能发生的骚乱。最近的示威活动 致癌病毒可能的转化蛋白在结构上是 与生长因子或其细胞表面受体相关，提供 几种可能的致癌机制可能是由一种变化引起的 在正常生理关系中的生长因子及其特异性 细胞受体。例如，某些淋巴组织肿瘤，如 B细胞白血病，是由于产生令人讨厌的生长因子或 来自失去正常控制序列的受体，或来自受体 与B细胞生长因子结合并发生反应，但不再能结合或 对B细胞分化因子的反应，将直接 一次测定免疫中淋巴细胞的结合方式 系统对他们的生理配体进行了分析，如建议的那样 在这项研究中。