ONTOGENETIC DEVELOPMENT OF LYMPHOCYTES

淋巴细胞的个体发育

• 批准号: 3176440
• 负责人: ULRICH G HAMMERLING
• 金额: $ 26.92万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3176440
• 关键词: B lymphocyte; RNA; affinity chromatography; antibody; autoradiography; biological polymorphism; cell differentiation; clone cells; crosslink; electrofocusing; flow cytometry; gel electrophoresis; gel filtration chromatography; gene expression; genetic manipulation; genetic translation; helper T lymphocyte; high performance liquid chromatography; histochemistry /cytochemistry; histocompatibility antigens; histocompatibility gene; hybridomas; immunochemistry; immunogenetics; interferons; interleukin 2; isoantibody; leukocyte activation /transformation; linkage mapping; lymphocyte; macrophage; membrane activity; mitomycins; mixed tissue /cell culture; molecular cloning; monoclonal antibody; nuclease; phosphorylation; radiotracer; suppressor T lymphocyte; surface antigens; thymus; tumor necrosis factor alpha

The Ly-6 group of alloantigens is one example of cell-surface antigen systems which are encoded by multigene families. At least five distinct Ly-6 antigens named Ly-6A, B, C, D and Th B have been identified by us and others. Decisive progress in the biochemical and serological characterization of these antigens strongly supports our working hypothesis of close structural relationships between the Ly-6 antigens. Direct support is rendered by analysis at the DNA level with the first Ly-6 cDNA probe available, which has confirmed the existence of multiple cross-hybridizing Ly-6DNA sequences in the mouse genome. The other breakthrough was the demonstration in several laboratories, including ours, that Ly-6.A antigens are important modulators allied with T cell activation, thus providing for the first time clues regarding the physiological role of Ly-6 for lymphocytes. In view of these new developments our project on the immunogenetics of Ly-6 will be redefined as follows: we will 1) Analyse the Ly-6A and related genes in detail, 2) Continue cellular immunological studies of Ly-6 using normal cells and cloned cell lines to test the hypothesis that Ly-6 is a signal modulator in cellular activation, 3) Continue the biochemical characterization of Ly-6 proteins to determine glycosylation and phosphorylation status and their form of plasma membrane association, 4) Look for Ly-6 involvement in multimolecular complexes on the cell surface, 5) Following the finding that Ly-6A is selectively induced by interferon, study modulation of Ly-6 antigen and gene expression by lymphokines on T cell, B cells and NK cells and correlate this with functional responses.

Ly-6组同种异体抗原是细胞表面的一个例子 由多基因家族编码的抗原系统。在… 至少五种不同的Ly-6抗原，分别命名为Ly-6A、B、C、D和ThB 已经被我们和其他人确认了。取得了决定性的进展 这些抗原的生化和血清学特征 有力地支持了我们关于封闭结构的工作假说 Ly-6抗原之间的关系。直接支持是 通过与第一个Ly-6 cDNA在DNA水平上的分析呈现 探测器可用，已确认存在多个 小鼠基因组中Ly-6DNA序列的交叉杂交。这个 另一个突破是在几个方面的演示 实验室，包括我们的实验室，认为Ly-6A抗原很重要 调节剂与T细胞激活结合在一起，从而为 首次关于Ly-6在脑内的生理作用的线索 淋巴细胞。 鉴于这些新的发展，我们的项目 Ly-6的免疫遗传学将重新定义如下：我们将 1)对Ly-6A及相关基因进行详细分析， 2)用正常细胞进行Ly-6细胞免疫学研究 细胞和克隆的细胞系来验证Ly-6是一种 细胞激活中的信号调制器， 3)继续Ly-6蛋白的生化特性 测定糖基化和磷酸化状态及其相互关系 质膜缔合形式， 4)寻找Ly-6参与多分子络合物 细胞表面， 5)在发现Ly-6A选择性地被 干扰素，研究Ly-6抗原和基因表达的调节 T细胞、B细胞和NK细胞上的淋巴因子及其相互关系 有功能反应。