The Kell blood group is one of the major antigenic systems in human red cells. It is a complex system and currently 23 alloantigens have been determined to be part of, or related to, this group. It is clinically important because it is a EBT strong immunogen and incompatibility involving Kell blood group antigens can cause severe hemolytic reactions in the newborn. 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. McLeod persons also have accompanying muscular dystrophy and neurological abnormalities indicating that the cellular defect is not confined to erythroid cells. We have identified and partially characterized a unique 93,000 dalton transmembrane glycoprotein that carries Kell antigens and have demonstrated that Kx resides on a different 37,000 dalton protein. We now plan to fully characterize the Kell blood group protein, analyzing its carbohydrate structure and obtaining its primary structure by sequencing its cDNA. The characteristics which determine different Kell phenotypes will be investigated. The Kell gene will be isolated and its organization studied. Because of the relationship between Kell and Kx and the implication that Kx may be involved in maintaining shape and function of cells other than erythrocytes, we shall further characterize the 37,000 dalton protein. Using cloning techniques Kx cDNA will be prepared and sequenced and the structure of Kx gene in normal and McLeod DNA will be elucidated. Preliminary evidence indicate that McLeod red cell acanthocytes have an imbalance in lipid bilayer asymmetry. The biochemical cause of this defect will be determined.
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