HLA CLASS II GENES; REGULATION OF EXPRESSION

主要组织相容性复合体（MHC）抗原，HLA抗原 在人类中，它们在产生，调节， 并对外来抗原产生免疫应答。 产品 II类基因以及相关的不变链， 主要在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。 虽然 已知II类抗原参与抗原呈递 和免疫反应的调节，也可能作为信号 对于分化，它们的功能还不完全清楚。 II类基因的调控必须进行微调。 异常或 不平衡的II类表达可能引发几种自身免疫性疾病 疾病，并可能帮助恶性细胞逃避免疫反应。 我们提出实验来确定所需的调控基因， 使用体细胞遗传学的II类表达。 另外我们 将研究转录控制的性质， 第二类产品的加工。 因为不同的组织 类型可能使用不同的机制来调节II类基因，我们 将分析B淋巴样细胞中的II类表达， 来自转移性黑素瘤的几种细胞系，其调节 第二类以不同的方式表达。 这些系统被选中 因为它们可以让我们比较两种不同的监管方式 细胞谱系，并帮助我们确定控制是如何废除， 疾病状态。 HLA中至少编码三个同源基因亚组 II类区域，和几个基因的良好表征 II类抗原DP、DQ和DR已被克隆和分析。 我们将比较在每一个控制监管的机制， 亚基因座 此外，新的基因，如DZ，DO和DX， 已经发现了;而且可能还有其他基因 尚未在II类区域内确定。 我们分析 各II类亚基因座产物的组织分布，以及 检查他们的差异调节，将导致更好的 了解真核基因调控的机制。

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.