MURINE TLA GENES--ORGANIZATION, EXPRESSION, REGULATION

I类基因家族位于主要组织相容性 小鼠的MHC复合体，编码两大类蛋白质 产品：移植抗原和非经典或Ib类 抗原 移植抗原参与了 细胞毒性T淋巴细胞的外源抗原。 类lb的功能 抗原未知。 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， 在不同的小鼠品系之间是保守的。 有些是专门表达的， 或者说是淋巴组织中的最高水平。 几种蛋白质编码的 Tla/Hmt区域基因已被鉴定。 已经提出 Tla/Hmt区域基因已经进化为编码蛋白质， 鼠标中的特殊功能。 长期目标是 研究的目的是确定蛋白质编码的功能， 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、表达和调节， 他们的蛋白质产品是必需的。 目的一：克隆酵母人工染色体中的Tla/Hmt基因。 这将有助于绘制该区域的地图， 鉴定存在于该区域中的所有I类基因。 在Aim II中，将产生针对合成肽的抗体， 从几种Ib类蛋白质的预测氨基酸序列， 将用于鉴定和表征这些蛋白质。 所述肽 抗体和基因特异性寡核苷酸探针将用于 确定哪些组织和哪些细胞亚群 组织，表达单独的I类基因。 在目标III中，我们将研究参与的分子机制。 一个编码胸腺白血病的Tla/Hmt区基因的调控 抗原的 顺式作用元件和蛋白质与这些相互作用 将使用功能分析和最先进的 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， 确定这些功能可能会导致复杂的进一步定义 参与脊椎动物免疫反应的细胞相互作用。

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.