EXPRESSION OF HUMAN CLASS II ANTIGENS

人类主要组织相容性复合体具有两组 广泛多态性基因称为I类和II类基因。 从这些基因衍生的分子在基因组中起着关键作用。 外来抗原的免疫识别。 各种等位基因形式的 II类基因与几种疾病有关，大多数 自身免疫性疾病 深刻认识 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。 II类基因的数量和表达，特别是 将检查DX、DX和DO基因座。 将努力 以分别鉴定DZ β和DO α基因。 共- 分别表达DX α和DO β cDNA克隆， 候选DZ β和DO α基因和cDNA克隆可 找出缺失的基因 因为可以预期， 分子是非多态性的，它不能作为限制性的分子。 抗原呈递元件 它被承认的可能性 而不是T细胞受体 通过分析可溶性DO分子与 合适的细胞类型。 DX基因对显示出所有特征 预期的功能基因，但转录本还没有 鉴定 可能存在的沉默序列， 阻止DX基因在检测的细胞类型中表达 将通过内含子序列的缺失突变来探索 随后转染并测量转录物 合成. II类基因的遗传多态性可能是 由表型多态性补充， 来自不同基因座的链的异二聚体形成。 的 这种混合II类分子的存在将在 HeLa细胞转染的各种组合的表达 载体插入的cDNA。 这些分子在同基因遗传中的作用 和同种异体MLR也将进行研究，目的是探索 是否存在对它们和DX的免疫耐受性， DO和DZ分子与免疫耐受是否存在 对它们和DX、DO和DZ分子以及是否是线性的 或构象决定簇负责MLR 反应性 详细了解类的功能 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克隆产生， 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.