BIOLOGY OF THE HUMAN GLYCOPHORIN BLOOD GROUP ANTIGENS

血糖素A是人红细胞表面的主要糖蛋白 并含有一个N-糖链和多个O-糖链。血糖素B，一种高度 人红细胞上的同源糖蛋白，只含有O-糖链。 尽管适当的糖基化对细胞表面的表达是至关重要的 在血糖素A中，导致这种作用的机制不是 明白了。血糖素A和B在实践中很重要 输血医学因为它们携带多种人类血型抗原， 而针对这些抗原的抗体可以引起溶血性输血反应， 新生儿溶血性疾病、自身免疫性溶血性贫血。 然而，很少有研究检验这种病毒的细微特异性。 人多克隆抗体和鼠单抗与这些抗体的结合 分子。血糖素A和B在医学上也很重要，因为 它们是疟原虫入侵时的红细胞表面受体 恶性疟原虫裂殖子。由于很难获得突变体 在氨基酸序列中具有特定变体的血糖素分子和 低聚糖的结构，对这种宿主细胞的详细了解- 寄生虫之间的相互作用目前还不可用。当前的目标是 建议研究细胞生物学、免疫学和受体功能 人类血型糖蛋白抗原： 1.确定N-葡聚糖和O-葡聚糖在 血糖素A的细胞内转运 2.用重组dna方法检测小鼠和人的免疫。 对血糖素A和B的反应，以及 3.测定血糖素A和糖的多肽和碳水化合物部分 B是被人类疟疾寄生虫识别的。 这些目标将通过使用一系列稳定转染的细胞来实现 表达野生型或变异型血糖素A或B的新品系 突变的血糖素A和B的cDNA将通过定点构建 诱变。B=y在正常中国仓鼠卵巢中的表达 成纤维细胞和那些糖基化缺陷的细胞，有可能 创造不同的血糖素，在氨基酸和 碳水化合物序列。噬菌体展示文库将被构建为 检查小鼠对血糖素A的免疫反应，这将确定 免疫反应是否受到限制，是否也会导致急性呼吸衰竭 构建新的临床实用的血清学试剂。总而言之， 这些研究将使人们更好地理解细胞生物学， 血糖素A和B的免疫学和受体功能。

Glycophorin A is the major glycoprotein on the human erythrocyte surface and contains one N-glycan and multiple O-glycans. Glycophorin B, a highly homologous glycoprotein on human erythrocytes, contains only O-glycans. Although appropriate glycosylation is crucial for cell surface expression of glycophorin A, the mechanism responsible for this effect is not understood. Glycophorin A and B are important in the practice of transfusion medicine since they carry multiple human blood group antigens, and antibodies to these antigens can cause hemolytic transfusion reactions, hemolytic disease of the newborn,a nd autoimmune hemolytic anemia. However, there have been few studies examining the fine specificity of binding of human polyclonal and mouse monoclonal antibodies to these molecules. Glycophorins A and B are also of medical importance because they serve as erythrocyte surface receptors for the invasion of Plasmodium falciparum malaria merozoites. Due to the difficulty in obtaining mutant glycophorin molecules with defined variaitons in amino acid sequence and oligosaccharide structure, a detailed understanding of this host cell- parasite interaction is not yet available. The goals of the current proposal are to study the cell biology, immunology, and receptor function of the human blood group glycophorin antigens by: 1. determining the role that the N-glycans and O-glycans play in intracellular transport of glycophorin A. 2. using recombinant DNA approaches to examine the murine and human immune response to glycophorins A and B, and 3. determining the peptide and carbohydrate portions of glycophorins A and B that are recognized by human malaria parasites. These goals will be achieved by using a series of stably transfected cell lines expressing cDNA of wild type or variant glycophorin A or B. New mutant glycophorin A and B cDNAs will be constructed by site-directed mutagenesis. B=y expressing the cDNAs in both normal Chinese hamster ovary fibroblasts and those with defects in glycosylation, it is possible to create variant glycophorins that differ in both amino acid and carbohydrate sequence. Phage display libraries will be constructed to examine the murine immune response to glycophorin A. This will determine whether the immune response is restricted and will also result in athe construction of new clinically useful serological reagents. In summary, these studies will result in greater understanding of the cell biology, immunology, and receptor function of glycophorins A and B.