NON H 2 HISTOCOMPATIBILITY GENES AND ANTIGENS

实体器官和骨髓移植已被证明是可行的 治疗人类疾病，如肾、心、肝和肺 疾病和癌症。然而，成功的主要障碍是 供者和受者之间同种异体抗原引起的免疫排斥反应 收件人。次要（H）组织相容性抗原，由 许多基因座分散在整个基因组中，在 这种排斥过程是当个体与HLA匹配时发生的。从小到大 H基因只能通过其同种抗原来鉴定，主要是 关于这种小H基因座产生的机制的问题 它们的次要H抗原仍未得到解决。我们的总体目标是 阐明这些机制。我们建议继续进行分子 概念上重要的小鼠小H基因编码的表征 小鼠2号染色体位点H3和Y染色体位点Hya。 H3和Hya都是复杂的单倍型，无论是在功能上， 基因水平。我们首先关注H3，分析H3 a基因， 编码（或控制）MHC I类限制性H2 Db决定簇 由细胞毒性T细胞（CTL）识别。我们将克隆这个基因， 鉴定它，并确定它如何控制H3 a次要H抗原。 这项研究将提供一个详细的表征常染色体- 编码小H基因，其免疫显性抗原刺激CTL。我们 然后克隆并鉴定编码（或控制）MHC的H3 b II类限制性H2 Ab决定簇被辅助性T细胞（TH）识别。 这是一个特别感兴趣的基因， (IR)控制细胞毒性T细胞反应的基因。该分析将 提供了一个次要H基因的第一个特征， 协调对其他次要H抗原的免疫应答。最后我们 将分析Hya，重点澄清一个有趣的形式， 遗传控制，其中Y编码基因Smcy可控制雄性特异性 (HY)由不同基因编码的小H肽。总体而言，这些 研究应该提供许多新的见解的分子基础 小H抗原，以及它们被激活的遗传机制。 控制。

Solid organ and bone marrow transplantation has proven to be a feasible treatment for human afflictions, such as kidney, heart, liver, and lung disease, and cancer. The primary obstacle to success, however, is immunological rejection caused by alloantigenic between the donor and recipient. Minor (H) histocompatibility antigens, which are encoded by numerous loci scattered throughout the genome, figure prominently in this rejection process when individuals are matched for HLA. Since minor H genes are identified only by virtue of their alloantigens, major questions concerning the mechanisms by which such minor H loci produce their minor H antigens remain unresolved. Our overall goal is to elucidate these mechanisms. We propose to continue the molecular characterization of conceptually important mouse minor H genes encoded by the mouse Chromosome 2 locus, H3, and the Y-chromosome locus, Hya. H3 and Hya are both complex haplotypes, both at the functional and genetic level. We will first focus on H3, and analyze the H3a gene, which encodes (or controls) MHC class I-restricted H2Db determinants recognized by cytotoxic T cells (CTL). We will clone this gene, characterize it, and determine how it controls the H3a minor H antigen. This study will provide a detailed characterization of an autosomally- encoded minor H gene whose immunodominant antigen(s) stimulate CTL. We will then clone and characterize H3b, which encodes (or controls) MHC class II-restricted H2Ab determinants recognized by helper T cells (TH). This is a gene of particular interest in that acts as an immune response (IR) gene that controls cytotoxic T cell responses. This analysis will provide the first characterization of a minor H gene that acts by orchestrating immune response to other minor H antigens. Finally, we will analyze Hya, focusing the clarification of an intriguing form of genetic control in which Y encoded gene, Smcy, may control male-specific (HY) minor H peptides encoded by distinct gene(s). Overall, these studies should provide many new insights into the molecular basis of minor H antigens, and the genetic mechanisms by which they are controlled.