Developmentally Regulated Glycosylation of the CD8αβ Coreceptor Stalk Modulates Ligand Binding

The functional consequences of glycan structural changes associated with cellular differentiation are ill defined. Herein, we investigate the role of glycan adducts to the O-glycosylated polypeptide stalk tethering the CD8αβ coreceptor to the thymocyte surface. We show that immature CD4+CD8+ double-positive thymocytes bind MHCI tetramers more avidly than mature CD8 single-positive thymocytes, and that this differential binding is governed by developmentally programmed O-glycan modification controlled by the ST3Gal-I sialyltransferase. ST3Gal-I induction and attendant core 1 sialic acid addition to CD8β on mature thymocytes decreases CD8αβ-MHCI avidity by altering CD8αβ domain-domain association and/or orientation. Hence, glycans on the CD8β stalk appear to modulate the ability of the distal binding surface of the dimeric CD8 globular head domains to clamp MHCI.