Glycan Ligand Specificity of Killer Lectin Receptors

Abstract

  Sialyl Lewis X (sLeX) antigen, Neu5Acα2,3Galβ1,4(Fucα1,3)GlcNAc-R, is expressed on the glycoproteins in sera or the surface of the cells and the expression of sLeX is enhanced in various conditions such as the inflammation and cancer. SLeX in the serum is utilized as a tumor marker. To clarify the roles of sLeX on secreted glycoproteins in vivo, we investigate the regulation of natural killer (NK) cell-dependent cytotoxicity through sLeX. NK cells express many receptors to kill the target cells such as cancerous cells and non-self, and their protein ligands have been elucidated. Of the killer lectin-like receptors (KLRs) on NK cells, several have been reported to recognize glycans. Using recombinant extracellular domains of KLRs (rKLRs: rNKG2A, C, D and rCD94), we evaluated their glycan ligand specificity and binding affinities using EIA methods. We clarified that all of these rKLRs can bind to high sLeX-expressing glycoprotein and heparin, heparan sulfate and highly sulfated polysaccharides and that glycan binding sites on NKG2D are mostly overlapped with those of protein ligands. In this review, we show the recent findings concerning the glycan ligands of these KLRs.