BIOCHEMICAL STUDIES OF HUMAN T CELL SURFACE MARKERS

T细胞分化是在胸腺微循环的影响下发生的。 骨髓来源的祖细胞增殖的环境 分化生成具有免疫活性的T淋巴细胞。主 本方案的目的是研究CD3-1的表达调控。 为胸腺内奠定基础的Gamma、Delta和epsilon基因 它们通过调控细胞表面T细胞的表达而分化 细胞受体/CD3复合体(TCRalphabeta/CD3Gammadeltaepsilonzeta2或 TCRGammadelta/CD3Gammadeltaepsilonzeta2)。 CD3-γ、-β和-epsilon的第一个主要功能在于其 参与TCR/抗原/MHC的信号转导 互动。但是，尽管在分子解剖学方面取得了快速的进展， TCR/CD3复合体，对其生化机制还有许多需要了解的地方 信号转导。CD3蛋白的另一个主要功能 调节TCR/CD3复合体的细胞表面组装。在 成熟、有功能的T淋巴细胞多链TCR/CD3复合体 是围绕由CD3-伽马，增量， 埃普西隆。T细胞受体α和β(或TCRγ和增量)是 随后添加到CD3-γ、-β、-epsilon核中，从而 促进杂二聚体的形成和二硫键的形成。最后， CD3-Zeta被添加到五聚体α、β、伽马、三角洲、epsilon中 亚复合体。 CD3-Delta、-Delta和-epsilon是仅有的已知的 在所有T细胞系中表达，但在任何其他细胞类型中不表达。我们的 因此，人们对CD3-Gamma，-Delta，epsilon基因簇感兴趣 不仅在其基因产物的重要功能上，而且在 它们表达的独特发育调节。这是有道理的 CD3基因不仅是胸腺发育的关键标志，而且 也是致力于T血统的必要条件。 这项建议的具体目的是： 1.研究CD3-Delta基因T细胞特异性转录调控。 2.研究控制T细胞特异性的分子机制 CD3-epsilon基因的表达。 3.鉴定参与该基因表达的转录元件 T细胞中的CD3-γ基因。 4.研究CD3-γ、-β、-epsilon的配位调节 胸腺内分化过程中的基因。

T cell differentiation occurs under the influence of the thymic micro- environment within which bone marrow derived progenitor cells proliferate and differentiate to generate immunocompetent T lymphocytes. The main objective of this proposal is to study regulation of expression of the CD3- gamma, delta, and epsilon genes which set the stage for intrathymic differentiation through their control of cell surface expression of the T Cell Receptor/CD3 Complex (TCRalphabeta/CD3gammadeltaepsilonzeta2 or TCRgammadelta/CD3gammadeltaepsilonzeta2). The first major function of CD3- gamma, -delta and -epsilon lies in their involvement in transduction of the signal caused by TCR/antigen/MHC interactions. But, despite rapid progress in the molecular anatomy of the TCR/CD3 Complex, much needs to be learned about the biochemical mechanisms of signal transduction. The other principal function of the CD3 proteins is in regulation of cell surface assembly of the TCR/CD3 Complex. In the mature, functionally competent T lymphocyte the multi-chain TCR/CD3 Complex is constructed around a protein core consisting of CD3-gamma, delta, epsilon. T Cell Receptor alpha and beta (or TCR gamma and delta) are subsequently added to the CD3-gamma, -delta, -epsilon core thus facilitating the heterodimer formation and disulfide linkage. Finally, CD3-zeta is added to the pentameric alpha,beta,gamma,delta,epsilon subcomplex. The CD3-delta, -delta and -epsilon are the only known genes that are expressed in all cells of T lineage, but not in any other cell type. Our interest in the CD3 -gamma, -delta, epsilon genes cluster lies therefore not only in the important functions of their gene products, but also in the unique developmental regulation of their expression. It is plausable that the CD3 genes are not only critical markers for thymic development, but are also sine qua non for commitment to the T lineage. The SPECIFIC AIMS of this proposal are to: 1. Study T cell specific transcriptional regulation of the CD3-delta gene. 2. Investigate the molecular mechanisms that govern T cell specific expression of the CD3-epsilon gene. 3. Characterize transcriptional elements involved in expression of the CD3-gamma gene in T cells. 4. Examine the coordinate regulation of the CD3-gamma, -delta, -epsilon genes during intrathymic differentiation.