KELL BLOOD GROUP SYSTEM AND THE MCLEOD PHENOTYPE

Kell血型是人类主要的血液抗原系统之一 红细胞 这是一个复杂的系统，目前有超过20种同种抗原 被认为是这个群体的一部分，或者与这个群体有关。 Kell系统 在输血医学中很重要，因为它的一些抗原 强免疫原和Kell抗体可引起严重反应， 输注不相容血液也会导致溶血性疾病， 新生儿由于母亲的免疫接种。 一个变体Kell系统 表型，命名为McLeod，其特征在于弱Kell抗原，缺乏 一种其他通用抗原Kx和严重异常的红细胞 形态学 McLeads还伴有迟发性肌营养不良症 和神经系统异常 我们已经鉴定出 携带Kell和Kx抗原，并通过分子克隆表征了 凯尔·吉恩。 我们现在有以下目标：1）在描述了19个 外显子和侧翼内含子区的凯尔基因，我们将确定 不同凯尔表型的分子基础 表型将是 通过转染细胞中抗原的表面表达证实。 这 信息将与项目5合作应用，以设计 用于鉴定Kell抗原的临床有用的方法， 抗体的 初步研究表明，患有罕见Ko（null）的人 表型，不表达任何Kell抗原或在细胞表面具有Kell蛋白的人。 红细胞膜含有具有正常编码序列的mRNA。 我们 将确定红细胞上缺乏Kell蛋白的原因， Ko（null）persons. 2)Kell蛋白具有序列和结构 与锌中性内肽酶相似。 我们将确定 Kell蛋白的酶特异性，并探索可能的功能。 3)我们将研究凯尔组装的细胞机制 在质膜上，重点是表达的起始和水平 在红细胞生成过程中。 4)McLeod综合征的候选基因（XK） 被隔离了 我们将确定它是否表达Kx表面- Kell与XK的关系。

The Kell blood group is one of the major blood antigenic systems in human red cells. It is a complex system and currently over 20 alloantigens have been determined to be part of, or related to, this group. The Kell system is important in transfusion medicine because some of its antigens are strong immunogens and Kell antibodies can cause severe reactions if incompatible blood is transfused and also cause hemolytic disease in newborns due to fetomaternal immunizations. A variant Kell system phenotype, named McLeod, is characterized by weak Kell antigens, lack of an otherwise universal antigen, Kx, and grossly abnormal red cell morphology. McLeads also have accompanying late onset muscular dystrophy and neurological abnormalities. We have identified the proteins that carry Kell and Kx antigens and by molecular cloning have characterized the Kell gene. We now have the following objectives: 1) Having characterized the 19 exons and the flanking intron regions of the Kell gene we will determine the molecular basis of different Kell phenotypes. The phenotypes will be confirmed by surface-expression of antigens in transfected cells. This information will be applied in collaboration with Project 5, to devise clinically useful procedures for identification of Kell antigens and antibodies. Preliminary studies show that persons with the rare Ko(null) phenotype, who do not express any Kell antigens or have Kell protein on the red cell membranes, contain an mRNA with normal coding sequences. We will determine the reasons for lack of Kell proteins on the red cells of Ko(null) persons. 2) Kell protein has sequence and structural similarities with zinc neutral endopeptidases. We shall determine the enzymatic specificities of Kell protein and explore possible functions. 3) We will investigate the cellular mechanisms by which Kell is assembled on the plasma membrane with emphasis on the onset and levels of expression during erythropoiesis. 4) A candidate gene (XK) for the McLeod syndrome has been isolated. We will determine whether it expresses Kx surface- antigen and study the relation between Kell and XK.