EXPRESSION OF HUMAN CLASS II ANTIGENS

人类主要组织相容性复合体含有两组 广泛多态的基因称为I类和II类基因。 从这些基因衍生出来的分子在 对外来抗原的免疫识别。多种等位基因形式 第二类基因与几种疾病有关，大多数 有自身免疫性的病因学。对…的深刻理解 II类分子及其基因的生理功能 需要了解它们在自身免疫性疾病中的作用。 第二类基因的数量和表达特别是与 将检查DX、DX和DO基因座。我们会作出努力 分别鉴定DZβ基因和DOα基因。共同-- 分别表达DXα和DOβ基因克隆， 与候选的DZβ和DOα基因和cDNA克隆可能 找出缺失的基因。因为可以预料到DO 分子是非多态的，它可能不会成为限制 抗原呈递元件。它被承认的可能性 通过另一种类型的受体而不是T细胞受体 通过分析可溶性DO分子与DO的结合来探索 适当的单元类型。DX基因对表现出所有的特征 预期的功能基因，但转录本尚未得到 已确认身份。消音器序列的可能存在 阻止DX基因在所检查的细胞类型中的表达 将通过内含子序列的缺失突变来探索 接下来是转录本的转染和检测 综合。II类基因的遗传多态可能是 由产生的表型多态补充 来自不同基因座的链异二聚体的形成。这个 这种混合的第二类分子的存在将在 不同表达组合的HeLa细胞 载体插入的cDNA。这些分子在同源基因中的作用 同种异体MLR也将进行研究，目的是探索 它们和DX是否存在免疫耐受， DO和DZ分子与是否存在免疫耐受 对于它们和DX、DO和DZ分子，以及是否线性 或构象决定因素对MLR负责 反应性。对班级功能的详细了解 Ii分子需要了解它们的三维结构 结构。适用于此类分析的可溶性II类分子 将通过表达突变的cdna克隆在 杆状病毒表达系统。拟议的研究将进一步 我们对人类II类分子表达的理解 并可能揭示免疫系统如何 在移植排斥的情况下识别这些分子。

The human major histocompatibility complex harbors two sets of extensively polymorphic genes called class I and class II genes. The molecules derived from these genes have pivotal roles in the immune recognition of foreign antigens. Various allelic forms of the class II genes are associated with several diseases, most of which have an autoimmune etiology. A profound understanding of the physiological function of the class II molecules and their genes is required to understand their role in autoimmune diseases. The number and expression of class II genes with special regard to the DX, DX and DO loci will be examined. Efforts will be made to identify a DZ beta and a DO alpha genes, respectively. Co- expression of DX alpha and DO beta cDNA clones, respectively, with candidate DZ beta and DO alpha genes and cDNA clones may identify the missing genes. Since it may be expected that the DO molecule is non-polymorphic it may not serve as a restricting antigen-presenting element. The possibility that it is recognized by another type of receptor than the T-cell receptor will be explored by analyzing the binding of soluble DO molecules to appropriate cell types. The DX gene pair exhibits all features expected of functional genes but transcripts have not been identified. The possible existence of silencer sequences that prevent expression of the DX genes in the cell types examined will be explored by deletion mutations of intron sequences followed by transfections and measurements of transcript synthesis. The genetic polymorphism of the class II genes may be complemented by a phenotypic polymorphism generated by heterodimer formation of chains derived from different loci. The existence of such hybrid class II molecules will be examined in HeLa cells transfected with various combinations of expression vector-inserted cDNAs. The role of such molecules in syngeneic and allogenic MLR will also be studied with the aims to explore whether immunological tolerance exists to them and to the DX, DO and DZ molecules and whether immunological tolerance exists to them and to the DX, DO and DZ molecules and whether linear or conformational determinants are responsible for the MLR reactivity. A detailed understanding of the function of the class II molecules required knowledge about their three-dimensional structure. Soluble class II molecules suitable for such analyses will be generated by expressing mutated cDNA clones in a baculovirus expression system. The proposed studies will further our understanding of the expression of human class II molecules and may reveal important aspects of how the immune system recognizes these molecules in transplant rejection situations.