ONTOGENETIC DEVELOPMENT OF LYMPHOCYTES

淋巴细胞的个体发育

• 批准号: 3176447
• 负责人: ULRICH G HAMMERLING
• 金额: $ 29.21万
• 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 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3176447
• 关键词: B lymphocyte; RNA; affinity chromatography; antibody; athymic mouse; autoradiography; biological polymorphism; cell differentiation; cell mediated lymphocytolysis test; chickens; clone cells; crosslink; electrofocusing; flow cytometry; gel electrophoresis; gel filtration chromatography; gene expression; genetic manipulation; genetic translation; glycosylation; helper T lymphocyte; high performance liquid chromatography; histochemistry /cytochemistry; histocompatibility antigens; histocompatibility gene; hybridomas; immunochemistry; immunogenetics; interferons; interleukin 1; interleukin 2; isoantibody; laboratory mouse; leukocyte activation /transformation; linkage mapping; lymphocyte; macrophage; membrane activity; membrane proteins; mitogens; mitomycins; mixed tissue /cell culture; molecular cloning; monoclonal antibody; natural killer cells; nuclease; nucleic acid probes; phosphorylation; protein structure; radiotracer; suppressor T lymphocyte; surface antigens; thymus; transfection; 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.

同种异体抗原的Ly-6组是细胞表面抗原的一个实例。 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，命名为Ly-6A、B、C、D和Th B 已经被我们和其他人发现了 决定性进展 这些抗原的生物化学和血清学表征 强烈支持我们的工作假设， Ly-6抗原之间的关系。 直接支助 通过在DNA水平上用第一个Ly-6 cDNA进行分析而呈现 探测器可用，已证实存在多个 交叉杂交小鼠基因组中的Ly-6DNA序列。 的 另一个突破是， 实验室，包括我们的，Ly-6.A抗原是重要的 与T细胞活化相关的调节剂，从而提供 关于Ly-6的生理作用的第一次线索， 淋巴细胞 鉴于这些新的事态发展， Ly-6的免疫遗传学将被重新定义如下：我们将 1)详细分析Ly-6A及相关基因， 2)使用正常人继续Ly-6的细胞免疫学研究 细胞和克隆的细胞系，以测试Ly-6是一种 细胞活化中信号调节剂， 3)继续Ly-6蛋白的生化表征 以确定糖基化和磷酸化状态及其 质膜结合的形式， 4)寻找Ly-6参与多分子复合物， 细胞表面， 5)在发现Ly-6A被选择性诱导之后， 干扰素对Ly-6抗原及基因表达调控的研究 通过T细胞、B细胞和NK细胞上的淋巴因子， 功能性反应。