Lewis (Le) blood group system phenotypes and genotypes

The Lewis blood group system in humans, designated with number 007 and symbol Le, consist of two different fucose containing carbohydrate antigen structures abbreviated Le^a+ (LE-1) and Le^b+ (LE-2). The expression of these two carbohydrate sequences are phenotype determinants. The Le^a+ antigen sequence is triasaccharide β-D-Galp-(1- 3)-[α-L-Fucp-(1-4)]-D-GlcpNAc. The Le^b+ antigen sequence is tetrasaccharide α-L-Fucp-(1-2)-β-D-Galp-(1-3)- [α-L-Fucp-(1-4)]-D-GlcNpAc. Biosynthesis of Le blood group glycan antigens is catalyzed by fucosyltransferase 2 (FUT2) and fucosyltransferase 3 (FUT3) enzymes. These enzymes are encoded by two dominant autosomal genes named FUT2, also referred as secretory (Se) gene, and FUT3, both having multiple alleles. These two genes determine Lewis blood group genotypes. Sequencing of fucosyltransferase genes, RNAs and fucosyltransferase enzymes and the determination of their structures, together with functional studies including spatial and temporal expression patterns, showed preservation of the catalytic domain within prokaryotes and eukaryotes, with a high level of diversity in structural and functional properties. Six different Le blood group phenotypes exist, taking in account that Le and ABO blood group antigens both comprise terminal sequences on the same branched glycan molecules: Le^a+b-, Le^a-b+, Le^a-b-, Le^a+b+, ALe^a-b+, and BLe^a-b+. Le antigens are part of glycan structures synthetized in glycolipids or glycoprotein form in the endoderm and not in the erythrocyte precursor cell. They are present on the cell surface of blood cells, in plasma and in secretory fluids. Le glycolipids are adsorbed from plasma on the cell surface of erythrocytes, platelets, lymphocytes and endothelial cells.