ANTIGENICITY OF GLOBULAR PROTEINS

球状蛋白的抗原性

• 批准号: 3480645
• 负责人: EMANUEL MARGOLIASH
• 金额: $ 17.5万
• 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 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3480645
• 关键词: B lymphocyte; T lymphocyte; antibody formation; antibody specificity; antigens; cell differentiation; clone cells; cytochrome c; globular protein; growth factor receptors; hybridomas; leukocyte activation /transformation; pigeons

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.

为了更好地了解抗体对T细胞的反应， 依赖性球蛋白抗原、一系列T细胞杂交瘤和B细胞 杂交瘤已经被开发出来，它可以与研究充分的主要 鸽细胞色素c抗原决定簇 在示威之后， T细胞只对蛋白质的肽段有反应， 幼稚B细胞，不管它们的特异性如何，都可以被刺激， 通过活化的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作为抗原是特别有效的选择，因为 蛋白质的化学性质是众所周知的， 具有所需放射性的任何所需初级结构的材料， 荧光和光亲和标记。 使用这样的配体，其旨在 定量研究T细胞抗原肽与细胞的结合， 表面II类分子的T细胞，导致其激活。 同样，B细胞生长和分化的协同结合 因子，由活化的T细胞和B细胞抗原（完整的 天然蛋白质），B细胞，使它们增殖和成熟， 抗体分泌细胞，将被定量检查。 的机制 免疫系统的细胞通过与它们的 生理学外部配体，从而被激活以产生所述组 这将使系统中的下一种细胞类型能够 由其外部配体激活，以在一种 控制的方式，提出了一个很好的和容易分析的模型， 生长因子与一般细胞生长的关系， 这种关系中可能出现的问题。 最近的示威活动， 致癌病毒的假定转化蛋白在结构上是 与生长因子或其细胞表面受体相关， 几种可能的致癌机制可能是由于 在正常的生理关系的生长因子和他们的具体 细胞受体 例如，某些淋巴瘤，如 B细胞白血病，由异常生长因子或 从失去正常控制序列的受体，或从受体 结合并与B细胞生长因子反应，但不再结合或 与B细胞分化因子反应，将直接 一旦确定免疫细胞的淋巴细胞的结合方式， 系统，其生理配体将被分析，如建议 本研究