BIOCHEMICAL STUDIES OF HUMAN T CELL SURFACE MARKERS

真核细胞的分化涉及精确协调的变化 几组基因的转录和翻译。 最终 T淋巴细胞的分化阶段主要发生在 胸腺 T3/T细胞受体复合物，由可变的 T细胞受体的异二聚体（α和β链）和三个 恒定多肽（T3-γ、δ和Ep 3）仅在 成熟胸腺细胞的表面。 这座建筑群是不可或缺的， T细胞与抗原呈递细胞或靶细胞之间的相互作用 并且在T细胞活化的起始中起主要作用。 为了探索T3/T细胞受体复合物在细胞周期中的组装性质， T淋巴细胞成熟我们将分离编码这三种基因 T3/T的恒定多肽链（T3-γ、δ和Ep 3） 细胞受体复合物。 胸腺细胞亚群和T细胞 将分析白血病细胞的T3基因表达， T细胞受体α和β基因的表达以及T细胞 谱系特异性基因T4和TBeta。 T3/T细胞的组装 受体复合物将使用几种方法，包括 体细胞变异体的产生。 体外DNA转移技术 和定点诱变。 基因表达的调控 将通过一系列体外研究T3/T细胞受体复合物的活性。 实验 这些包括寻找组织特异性转录因子， 增强子元件。 决定发育规律的因素 T3/T细胞受体复合物将在体内研究， 使用小鼠/人杂合T3-γ、δ和ε的转基因小鼠 基因. 拟议中的转基因小鼠实验将导致 理解转录和翻译的协调 控制T谱系特异性基因。 从这些研究中获得的数据 也将有助于我们了解白血病和其他疾病 如免疫缺陷等。

Differentiation of eukaryotic cells involves precisely orchestrated changes in transcription and translation of several sets of genes. The final stages of differentiation of T lymphocytes occur primarily within the thymus gland. The T3/T cell receptor complex, consisting of a variable heterodimer of the T cell receptor (Alpha and Beta chains) and the three invariable polypeptides (T3-Gamma, Delta and Epsilon), is expressed only on the surface of mature thymocytes. This complex is indispensable for the interactions between T cells and antigen presenting cells or target cells and plays a major role in the initiation of T cell activation. To explore the nature of assembly of the T3/T cell receptor complex during T lymphocyte maturation we will isolate the genes coding for the three invariable polypeptide chains (T3-Gamma, Delta and Epsilon) of the T3/T cell receptor complex in humans and mice. Thymocyte subpopulations and T leukemic cells will be analyzed for expression of the T3 genes in relation to the expression of the T cell receptor Alpha and Beta genes and the T lineage specific genes T4 and TBeta. The assemblage of the T3/T cell receptor complex will be investigated using several approaches including the generation of somatic cell variants. In vitro DNA transfer techniques and site directed mutagenesis. The regulation of expression of the genes of the T3/T cell receptor complex will be studied by a series of in vitro experiments. These include the search for tissue specific transcriptional enhancer elements. The factors that determine the developmental regulation of the T3/T cell receptor complex will be studied in vivo by generating transgenic mice using mouse/human hybrid T3-Gamma, Delta and Epsilon genes. The proposed experiments with transgenic mice will lead to an understanding of the coordination of transcriptional and translational control of T lineage specific genes. The data obtained from these studies will also contribute to our knowledge of leukemogenesis and other disease states such as immunodeficiencies.