NON H 2 HISTOCOMPATIBILITY GENES AND ANTIGENS

实体器官和骨髓移植已被证明是可行的 治疗人类疾病的方法，如肾、心、肝、肺 疾病和癌症。然而，成功的主要障碍是 供者与供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 分散在基因组中的许多基因座，突出地出现在 当个体与人类白细胞抗原相匹配时，这一排斥过程。从小调开始 H基因只能通过它们的同种异体抗原来识别 关于这些微小H基因座产生机制的问题 它们的次要H抗原仍未被分解。我们的总体目标是 阐明这些机制。我们建议继续分子研究 编码概念上重要的小鼠次要H基因的特征 由小鼠2号染色体H3和Y染色体Hya组成。 H3和Hya都是复杂的单倍型，在功能和 遗传水平。我们首先关注H3，分析H3a基因， 它编码(或控制)MHC I类限制的H_2Db决定簇 由细胞毒性T细胞(CTL)识别。我们将克隆这个基因， 确定它的特征，并确定它是如何控制H3a微小H抗原的。 这项研究将提供一种常染色体- 编码小H基因，其免疫优势抗原(S)刺激CTL。我们 然后将克隆和鉴定编码(或控制)MHC的H3B 辅助性T细胞(TH)识别的II类限制性H_2Ab决定簇。 这是一种特别感兴趣的基因，它起着免疫反应的作用。 (IR)控制细胞毒性T细胞反应的基因。这一分析将 提供了第一个微小H基因的特征，该基因通过 协调对其他次要H抗原的免疫反应。最后，我们 将分析Hya，重点是澄清一种有趣的形式 Y编码基因Smcy可能控制雄性专一性的遗传控制 (Hy)由不同基因编码的次要H肽(S)。总的来说，这些 研究应该提供许多新的洞察力，以了解 次要H抗原及其形成的遗传机制 控制住了。

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.