BIOCHEMICAL STUDIES OF HUMAN T CELL SURFACE MARKERS

真核细胞的分化涉及精确的精心安排的变化 几组基因的转录和翻译。决赛 T淋巴细胞的分化阶段主要发生在 胸腺。T3/T细胞受体复合体，由一个变量组成 T细胞受体异源二聚体(Alpha链和Beta链)和三种 不变多肽(T3-Gamma、Delta和Epsilon)仅在 成熟胸腺细胞的表面。这个建筑群是不可缺少的 T细胞与抗原提呈细胞或靶细胞的相互作用 在启动T细胞活化中起主要作用。 探讨T_3/T细胞受体复合体的组装性质 T淋巴细胞成熟我们将分离这三个基因的编码 T3/T的恒定多肽链(T3-Gamma、Delta和Epsilon) 人类和小鼠的细胞受体复合体。胸腺细胞亚群与T细胞 将分析白血病细胞中T3基因的表达与 T细胞受体α、β基因的表达与T细胞 谱系特异性基因T4和TBeta。T_3/T细胞的聚集 受体复合体将使用几种方法进行研究，包括 体细胞变异的产生。体外DNA转移技术 和定点突变。基因表达的调控 将通过一系列体外实验对T3/T细胞受体复合体进行研究 实验。这些包括对组织特异性转录的搜索 增强剂元素。决定发育规律的因素 将通过在体内通过生成 人/鼠杂交种T_3-γ、Delta和Epsilon转基因小鼠 基因。拟议中的转基因小鼠实验将导致 对转录与翻译协调的认识 T细胞系特异性基因的调控。从这些研究中获得的数据 也将有助于我们对白血病和其他疾病的了解 免疫缺陷等国家。

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.