GENETIC AND STRUCTURAL ORGANIZATION OF HUMAN IA

在人类中由人类白细胞抗原-D区编码的多个B细胞同种异体抗原系统 主要组织相容性复合体已经被定义。这些通常是 称为Ia抗原。重组DNA研究表明，有许多 由于存在六个不同的Ia基因座，尽管生化和遗传学研究 只正式展示了其中三个人的表情。这个 由Ia基因座编码的分子表现出高度的多态 多种氨基酸序列在同种异型间的差异。这 多态在功能上表现为不同的同种异型 确定免疫反应性的差异。此外，许多疾病 表现出自身免疫特征，如类风湿性关节炎和 多发性硬化症与特定的Ia同种异型有关。我们希望 分析Ia分子间变异的分子基础 生化和重组DNA技术。更确切地说，我们希望 问下面的问题：一个不同的Ia分子可以有多少个 个人快递？不同Ia的分子关系是什么？ 同一个人体内的分子？分子间的关系是什么 人与人之间的Ia分子？我们相信这些研究将帮助我们 了解Ia分子如何调节免疫应答并确定 疾病易感性。

In man multiple B cell alloantigenic systems encoded by the HLA-D region of the major histocompatibility complex have been defined. These are often referred to as Ia antigens. Recombinant DNA studies suggest that as many as six distinct Ia loci exist, although biochemical and genetic studies have only formally demonstrated the expression of three of them. The molecules encoded by the Ia loci display a high degree of polymorphism due to multiple amino acid sequence differences among allotypes. This polymorphism is manifested functionally in that different allotypes determine differences in immune responsiveness. In addition many diseases that display autoimmune characteristics such as rheumatoid arthritis and multiple sclerosis are associated with particular Ia allotypes. We wish to analyze the molecular basis of variability among Ia molecules using biochemical and recombinant DNA techniques. More specifically we wish to ask the following questions: How many different Ia molecules can a single individual express? What are the molecular relationships of different Ia molecules within the same individual? What are the molecular relationships of Ia molecules between individuals? We believe these studies will help us to understand how Ia molecules regulate immune responsiveness and determine disease susceptibility.