ASSEMBLY AND FUNCTION OF THE T CELL RECEPTOR/CD3 COMPLEX

胸腺来源的淋巴细胞(T细胞)是 肠道相关淋巴组织(GALT)，并可能发挥突出作用 在一些肠道疾病的发病机制中。这些 包括炎症性肠病、传染性疾病等疾病 肠炎和移植物抗宿主病 T淋巴细胞增加，存在的T淋巴细胞被激活。在……里面 为了深入了解这些障碍，重要的是 了解T细胞功能的基本机制。A T细胞 识别已处理的标称抗原，与 主要组织相容性复合体(MHC)的组成 靶细胞表面通过T细胞受体(TCR)。TCR， 它同时辅助抗原和MHC识别，由以下组成 两种免疫球蛋白样蛋白，α和β或omega和 达美航空。与TCR非共价关联的是非变异体 CD3复合体的链；CD3 omega、Delta、epsilon和 可能在TCR结合后的跨膜信号转导中起重要作用 抗原/MHC。为了使T细胞对抗原/MHC作出反应 必须正确组装TCR/CD3的多肽链 并将它们输送到细胞表面。装配的 TCR/CD3复合体蛋白与T细胞功能 因此，是紧密相连的。这项研究的具体目的 是要(1)通过使用特定的转染法进行研究 在T细胞突变体和非T细胞中的cDNAs，描述该蛋白 TCR/CD3的组装和表面表达所需的链 复杂；(2)定义组装中重要的结构域和 定点突变体外表达基因的表面表达 饱和诱变及将改变后的基因转入 T细胞；(3)定义信号中重要的结构域 定点突变cDNAs的体外转导 饱和诱变及其特异性限制 核酸内切酶并将改变的cDNAs导入T细胞和 (4)鉴定T细胞活化突变体的功能缺陷 通过将正常的cDNAs导入T细胞突变体和 指导下的异常cDNAs的克隆和测序 考克斯·特霍斯特博士的这些研究将为调查者提供 在分子免疫学方面有丰富的经验。这 在未来，知识可以作为一种独立的 T细胞分化和研究的学术研究员 在高尔特中激活。

Thymus derived lymphocytes (T cells) ar a major component of the gut associated lymphoid tissue (GALT) and may play a prominent role in the pathogenesis of a number of intestinal disorders. These include such diseases as inflammatory bowel disease, infectious enteritides and graft-versus-host disease in which the number of T lymphocytes are increased and those present are activated. In order to gain an insight into these disorders, it is important to understand the fundamental mechanisms of T cell function. A T cell recognizes processed nominal antigens in association with the components of the major histocompatibility complex (MHC) on the surface of a target cell via the T cell receptor (TCR). The TCR, which subserves both antigen and MHC recognition, is composed of two immunoglobulin like proteins, alpha and beta or omega and delta. Noncovalently associated with the TCR are the nonvariant chains of the CD3 complex; CD3 omega, delta, epsilon, and , which may be important in transmembrane signaling after the TCR binds antigen/MHC. In order for a T cell to respond to antigen/MHC it must correctly assemble the polypeptide chains of the TCR/CD3 complex and transport them to the cell surface. Assembly of the protein of TCR/CD3 complex and functional competence of the T cell are, therefore, closely coupled. The specific aims of this study are to (1) through the use of transfection studies with specific cDNA's in T cell mutants and non-T cells, delineate the protein chains required for assembly and surface expression of the TCR/CD3 complex; (2) to define structural domains important in assembly and surface expression by mutating cDNA's in vitro with site directed and saturation mutagenesis and transfecting the altered cDNA's into T cells; (3) to define structural domains important in signal transduction by mutating cDNA's in vitro with site directed and saturation mutagenesis as well as with specific restriction endonucleases and transfecting the altered cDNA's into T cells and (4) characterize the functional defect in T cell activation mutants by transfection of normal cDNA's into the T cell mutants and cloning and sequencing the abnormal cDNA's. Under the direction of Dr. Cox Terhorst, these studies will provide the investigator with an extensive experience in molecular immunology. This knowledge can, in the future, be directly applied as an independent academic investigator to studies of T cell differentiation and activation in the GALT.