MOLECULAR BASIS OF BLOOD GROUP ANTIGENS

血型抗原的分子基础

• 批准号: 2857855
• 负责人: COLVIN M REDMAN
• 金额: $ 141.88万
• 依托单位: NEW YORK BLOOD CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-02-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2857855
• 关键词: blood group antigens; blood group incompatibility; erythrocyte membrane; genetic polymorphism; human subject; molecular pathology; surface antigens

The objectives are 1) To introduce, to the blood banking community, more exact and convenient methods for determining red cell antigens and identifying antibodies by studying the molecular basis of blood groups with emphasis on the identification of allelic variations. 2) To determine structure/function relationships of some red cell blood groups. 3) To link specific blood group genotypes with disease processes and to understand the basis for the disease. To accomplish these goals we have a collaborative program composed of five projects. Four projects investigate the molecular and cell biology of Rh (Project 1), Kell (Project 2), Duffy (Project 3) and Xg (Project 4) blood groups and project 5 is a clinical component which will apply molecular biology procedures to improving the detection of antibodies and antigens as practiced in a blood bank reference laboratory. Project 1 aims to construct a physical map of the entire Rh locus and determine the order, transcriptional orientation and expression of the major Rh genes. This will lead to understanding the molecular basis of many Rh-related antigens, which is important in blood transfusion, autoimmune hemolytic disease and in hemolytic disease of the newborn (HDN). Kell blood group system incompatibilities also present difficulties in blood transfusion and HDN. Kell antigens reside on a surface exposed glycoprotein with homology to zinc neutral endopeptidases. An aim of Project 2 is to determine the possible role of red cell surface peptidases. Duffy glycoprotein (gpFy), on red cells, acts as a chemokine receptor and also as a binding site for the human malarial parasite Plasmodium vivax. Duffy protein is also found in other tissues such as kidney, lung, thymus and brain. Project 3 aims to determine the function of gpFy in these tissues and, by studying the structure of gpFy, design ways to prevent P. vivax invasion. Project 4 will determine whether Xg blood group is involved in cell interactions. In addition to hematopoietic tissues Xg is found in fibroblasts and is homologous to a product of the MIC 2 gene. Project 5 will use synthetic and recombinant peptides, and allelic-specific transfectants to analyze antibodies in patients. Information on the molecular basis of Rh, Kell, Duffy and Xg blood groups (Projects 1-4) will also be used to introduce new procedures for the identification of blood group antigens. This will impact on pre- natal determination of whether a fetus is at risk for HDN and should be useful in screening for antigen-negative blood for certain immunized patients, such as those with Sickle Cell disease. The five projects are supported by three Core units; administrative, cell culture and cell sorting. The cell culture unit will provide training to investigators, isolate CD34+ cells from hematopoietic tissues, culture progenitor cells and prepare tested reagents for primary hematopoietic cultures. The cell sorting unit will sort and analyze, by flow cytometry, hematopoietic stem cells, committed progenitor cells and other hematopoietic cells with different degrees of differentiation. Overall these 5 projects provide an integrated approach to studying the molecular and cell biology of blood groups and applying the knowledge gained to modernize blood banking procedures and understand the functions of some blood groups and their possible relations to diseases.

目标是：1）向血库界介绍更多 用于测定红细胞抗原的准确和方便的方法， 通过研究血型的分子基础来识别抗体 重点在于鉴定等位基因变异。 2)到 确定一些红细胞血型的结构/功能关系。 3)将特定血型基因型与疾病过程联系起来， 了解疾病的基础。 为了实现这些目标，我们 一个由五个项目组成的合作项目。 四个项目 研究Rh的分子和细胞生物学（项目1），Kell （项目2），达菲（项目3）和Xg（项目4）血型和项目 5是一个临床部分，它将应用分子生物学程序， 改进在血液中实施的抗体和抗原的检测 银行参考实验室。 项目1的目的是建立一个物理地图 整个Rh基因座，并决定顺序，转录方向 和主要Rh基因的表达。 这将有助于理解 许多Rh相关抗原的分子基础，在血液中很重要 输血、自身免疫性溶血性疾病和 新生儿（HDN）。 凯尔血型系统不兼容也存在 输血困难和HDN。 Kell抗原存在于 与锌中性内肽酶同源的表面暴露糖蛋白。 项目2的目的是确定红细胞表面的可能作用， 肽酶 达菲糖蛋白（gpFy），红细胞上，作为一种趋化因子 受体，也作为人类疟疾寄生虫的结合位点 间日疟原虫 达菲蛋白也存在于其他组织中， 肾、肺、胸腺和脑。 项目3旨在确定 通过研究gpFy的结构， 防止间日疟原虫入侵的方法 项目4将决定Xg是否 血型与细胞相互作用有关。 除了 造血组织Xg存在于成纤维细胞中，并且与 MIC 2基因的产物。 项目5将使用合成和重组 肽和等位基因特异性转染子，以分析 患者 关于Rh、Kell、Duffy和Xg分子基础的信息 血型（项目1-4）也将用于引入新的程序 用于血型抗原的鉴定。 这将影响到预- 纳塔尔时确定胎儿是否有HDN风险， 可用于筛选某些免疫的抗原阴性血液， 患者，如镰状细胞病患者。 这五个项目是 由三个核心单位提供支持：行政、细胞培养和细胞 分类 细胞培养股将为研究人员提供培训， 从造血组织中分离CD 34+细胞，培养祖细胞 并准备原代造血培养的待测试剂。 细胞 分选单元将通过流式细胞术分选和分析造血干细胞， 细胞、定向祖细胞和其它造血细胞， 不同程度的分化。 总的来说，这5个项目提供了一个 研究血液分子和细胞生物学的综合方法 并应用所获得的知识使血库现代化 了解某些血型的功能及其 可能与疾病有关。