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。 红血球。这是一个复杂的系统，目前有20多个同种异体抗原 被确定为这一群体的一部分或与之相关的。凯尔体系 在输血医学中很重要，因为它的一些抗原 强免疫原和Kell抗体可在以下情况下引起严重反应 血型不合的输血也会引起溶血性疾病 因胎母免疫而产生的新生儿。一种变种的凯尔系统 表型，命名为McLeod，以弱Kell抗原为特征，缺乏 一种其他通用的抗原，Kx，和极不正常的红细胞 形态学。McLeads还伴有晚发性肌营养不良症 以及神经异常。我们已经鉴定出了 携带Kell和Kx抗原并通过分子克隆获得了 凯尔·基恩。 我们现在有以下目标：1)描述了19 我们将确定Kell基因的外显子和侧翼内含子区域 不同Kell表型的分子基础。表型将是 通过在转基因细胞中表面表达抗原来证实。这 信息将与项目5合作应用，以设计 临床上有用的鉴定Kell抗原和 抗体。初步研究表明，患有罕见KO(NULL)的人 表型，不表达任何Kell抗原或有Kell蛋白 红细胞膜含有一种具有正常编码序列的信使核糖核酸。我们 将确定红血球上缺乏Kell蛋白的原因 KO(空)人。2)Kell蛋白具有序列和结构 与锌中性内肽酶的相似性。我们将决定 Kell蛋白的酶特性并探索其可能的功能。 3)我们将研究Kell组装的细胞机制 关于质膜，重点是表达的起始和水平 在红血球生成过程中。4)McLeod综合征的候选基因(XK) 已经被隔离了。我们将确定它是否表示Kx曲面- 抗原，研究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.