MURINE TLA GENES--ORGANIZATION, EXPRESSION, REGULATION

I类基因家族位于主要组织亲和性 小鼠的复合体(MHC)，编码两大类蛋白质 品种：移植抗原及非经典或类Lb 抗原。移植抗原参与了肿瘤的呈递。 外来抗原对细胞毒T淋巴细胞的作用。Lb类的功能 抗原尚不清楚。24个Lb类基因已被定位到 BALB/c小鼠MHC的TLA/HMT区。这些基因非常 与移植抗原基因相比差异很大，但却高度一致 在不同的小鼠品系之间保守。有些是专门表达的， 或最高水平，在淋巴组织中。编码的几种蛋白质 已鉴定出TLA/HMT区基因。有议员建议， TLA/HMT区域基因已经进化到编码能够执行 鼠标中的特殊功能。这样做的长期目标是 研究是为了确定由编码的蛋白质的功能 TLA/HMT区基因。为了实现这一目标，基本信息 关于这些基因的组织、表达和调控 他们的蛋白质产品是必需的。 在目标I中，我们将克隆酵母人工染色体中的Tla/HMT区域。 这将有助于绘制这一区域的地图，并将允许 鉴定位于该区域的所有I类基因。 在AIM II中，将产生针对合成多肽的抗体 从预测的几类Lb蛋白的氨基酸序列和 将被用来鉴定和表征这些蛋白质。多肽 抗体和基因特异性寡核苷酸探针将用于 确定这些组织中的哪些组织和细胞亚群 组织，表达单独的I类基因。 在目标III中，我们将研究涉及到的分子机制 胸腺白血病编码基因Tla/HMT区基因的调控 抗原。与之相互作用的顺式作用元件和蛋白质 元素将使用功能分析和最新技术进行鉴定 分子生物学技术。 这些研究的结果将为今后的研究提供基础 确定功能可能会导致对复合体的进一步定义 脊椎动物免疫反应中的细胞相互作用。

The class I family of genes is located in the major histocompatibility complex (MHC) of the mouse and encodes two major groups of protein products: the transplantation antigens and the non-classical or class lb antigens. The transplantation antigens are involved in the presentation of foreign antigens to cytotoxic T lymphocytes. The function of the class lb antigens is not known. Twenty-four class lb genes have been mapped to the Tla/Hmt region in the MHC of the BALB/c mouse. These genes are very divergent compared to the transplantation antigen genes, yet are highly conserved between different mouse strains. Some are expressed exclusively, or a highest levels, in lymphoid tissues. Several proteins encoded by the Tla/Hmt region genes have been identified. It has been proposed that the Tla/Hmt region genes have evolved to encode proteins that perform specialized functions in the mouse. The long-term objective of this research is to determine the function of the proteins encoded by the Tla/Hmt region genes. To achieve this goal, fundamental information regarding the organization, expression and regulation of these genes and their protein products is needed. In Aim I, we will clone the Tla/Hmt region in yeast artificial chromosomes. This will facilitate mapping of this region and will permit the identification of all class I genes residing in the region. In Aim II, antibodies will be raised against synthetic peptides derived from the predicted amino acid sequences of several class lb proteins and will be used to identify and characterize these proteins. The peptide antibodies and gene-specific oligonucleotide probes will be used to determine which tissues and which subpopulations of cells within those tissues, express individual class I genes. In Aim III, we will study the molecular mechanism involved in the regulation of one Tla/Hmt region gene that encodes the thymus-leukemia antigen. Cis-acting elements and proteins that interact with these elements will be identified using functional assays and state-or-the-art molecular biological techniques. The results of these studies will provide a basis for future studies to determine the functions may lead to further definition of the complex cellular interactions involved in the vertebrate immune response.