HLA CLASS II GENES; REGULATION OF EXPRESSION

主要组织相容性复合体(MHC)抗原，人类白细胞抗原 在人类中，在产生、调节、 并对外来抗原产生免疫反应。的产品 第二类基因以及相关的不变链是 主要表达于B淋巴细胞、巨噬细胞、 但现在已经在许多其他类型的细胞上观察到了这种现象。虽然 已知第二类抗原参与抗原提呈。 和免疫反应中的调节，可能也是信号 对于分化，它们的功能还没有完全被理解。 对第二类基因的调控必须进行微调。反常的或 II类分子表达不平衡可能会引发几种自身免疫 疾病，并可能帮助癌细胞逃避免疫反应。 我们建议进行实验以确定所需的调控基因 利用体细胞遗传学进行II类表达。此外，我们 将调查转录和控制的性质 二类产品的加工。因为不同的组织 类型可能使用不同的机制来调节第二类基因，我们 将分析B淋巴样细胞中II类的表达 来自转移性黑色素瘤的几个细胞系 II类基因以不同方式表达。这些系统是被选中的 因为它们应该让我们比较两种截然不同的监管 细胞谱系并帮助我们确定如何在 疾病状态。 至少有三个亚组的同源基因在人类白细胞抗原中被编码 第二类区域，以及几个特征良好的基因 第二类抗原DP、DQ和DR已被克隆和分析。 我们将对控制监管的机制进行比较。 亚区块。此外，新的基因，如DZ，DO和DX，有 也有可能存在其他基因 在II类地区内尚未确定。我们对该事件的分析 各II类亚区块产物的组织分布，以及 审查他们的不同监管，将导致更好的 对真核基因调控机制的理解。

The major histocompatibility complex (MHC) antigens, HLA antigens in man, are of fundamental importance in generating, regulating, and effecting an immune response to foreign antigens. Products of the class II genes, as well as the associated invariant chain, are expressed primarily on the surfaces of B lymphocytes, macrophages, but now have been observed on many other types of cells. Although class II antigens are known to participate in antigen presentation and regulation in the immune response, and probably also as signals for differentiation, their functions are not completely understood. Regulation of class II genes must be finely tuned. Aberrant or imbalanced class II expression may trigger several autoimmune diseases and may help malignant cells evade an immune response. We propose experiments to identify regulatory genes required for class II expression using somatic cell genetics. In addition, we will investigate the nature of controls of transcription and processing of the class II products. Because different tissue types may use varying mechanisms to regulate class II genes, we will analyze class II expression in the B lymphoid cells and in several cell lines derived from metastatic melanomas which regulate class II expression in different ways. These systems were chosen because they should allow us to compare regulation in two distinct cell lineages and help us determine how controls are abrogated in disease states. At least three subgroups of homologous genes are encoded in the HLA class II region, and several of the genes for well characterized class Ii antigens, DP, DQ, and DR, have been cloned and analyzed. We will compare the mechanisms which control regulation at each sublocus. In addition, new genes, such as DZ, DO, and DX, have been found; and it is possible that there are other genes that are not yet identified within the class II region. Our analysis of the tissue distribution of each class II sublocus product, and examination of their differential regulation, will lead to a better understanding of the mechanisms of eukaryotic gene regulation.