NON H-2 HISTOCOMPATIBILITY GENES AND ANTIGENS

免疫系统中最鲜为人知的基本成分之一 系统功能是有机体维持的过程 对自身基因产物的耐受性和对病原体的反应性。一个 特别有希望的方法来理解这种微妙的 实现平衡的是对多态的非H-2基因的研究(次要的 组织亲和性(H)基因)，因为它们的产物 对基因不同的个体具有抗原性。使用这种方法 我们将解决两个关键问题：(1)这些类型的 基因是存在的，(2)它们的分子基础是什么？测定法 这些基因的数量将通过进行一项 育种和实验计划，将提供对 其产物可以刺激I类MHC的多态基因的数量- 限制性(细胞毒)T细胞(TC)和II类MHC限制性(辅助)T细胞 Cells(Th)来回答以下重要问题：是否有许多 或者是几个微小的H基因，其产物刺激Th和Tc？是否有重叠 或者由Th和Tc活性定义的微小H基因的随机分布？是 进化显著影响微小H基因的数量 距离还是MLS--差距？ 这些类型的基因的分子基础将分两部分来探讨。 方式。首先，基因转染实验将解决井是否- 定义基因β2-微球蛋白(B2M)是一种次要的H基因，其产物 被次要的H抗原特异性的Tc和Will识别为抗原 确定B2M抗原的分子基础。其次，TC将是 在基因转染实验中用作遗传探针 CDNA库和粘粒文库的筛选及微小H基因CDH-4的分离 其产品获得TC认可。随后的分子分析将 确定CDH-4基因的结构和CDH-4的分子基础 CDH-4的抗原性。这些研究将包括确定 抗原是否通过正常方式产生 转录事件或通过短的自主转录单位 (胡椒)。所获得的信息应该能澄清许多重要的问题。 关于微小的H基因，还将提供一种改进的方法 克隆其他基因，这些基因的产品可以激发T细胞活性。

One of the most poorly understood essential components of the immune system function is the process through which an organism maintains tolerance to self gene products and responsiveness to pathogens. A particularly promising approach to understanding how this delicate balance is achieved is study of polymorphic non H-2 genes (minor histocompatibility (H) genes) that can be detected because their products are antigenic to genetically different individuals. Using this approach we will address two critical questions: (1) How many of these types of genes are there and (2) what is their molecular basis? determination of the numbers of these genes will be approached by carrying out a breeding and experimental scheme that will provide an estimate of the numbers of polymorphic genes whose products can stimulate class I MHC- restricted (cytotoxic) T cells (Tc) and class II MHC-restricted (helper) T cells (Th) to answer the following significant questions: Are there many or few minor H genes whose products stimulate Th and Tc? Is there overlap or random distribution of minor H genes defined by Th vs. Tc activity? Are numbers of minor H genes significantly influenced by evolutionary distance or Mls- disparity? The molecular basis of these types of genes will be approached in two ways. First, gene transfection experiments will address whether the well- defined gene beta2-microglobulin (B2m) is a minor H gene whose products are recognized as antigen by minor H antigen-specific Tc and will determine the molecular basis of the B2m antigen. Second, Tc will be used as genetic probes in gene transfection experiments involving screening cDNA and cosmid libraries and isolating the minor H gene cdH-4 whose products are recognized by Tc. Ensuing molecular analysis will determine both the structure of the cdH-4 gene and the molecular basis of cdH-4 antigenicity. Included in these studies will be determination of whether the antigens are produces through normal transcriptional events or by short autonomous transcriptional units (peptons). The information obtained should clarify many important issues concerning minor H genes and will also provide a refined approach for cloning other genes whose products elicit T cell activity.