Sialic acid capping of CD8β core 1-O-glycans controls thymocyte-major histocompatibility complex class I interaction

Abstract

Bidentate interaction of a T-cell receptor and CD8αβ heterodimer with a peptide-MHCI complex is required for the generation of cytotoxic T-lymphocytes. During thymic development, the modification of CD813 glycans influences major histocompatibility complex class I binding to T-cell precursors called thymocytes. ES mass spectrometry (MS) and tandem MS/MS analysis were used to identify the changes occurring in the CD8β-glycopeptides during T-cell development. Several threonine residues proximal to the CD8β Ig headpiece are glycosylated with core-type 1 O-glycans. Non-sialylated glycoforms are present in immature thymocytes but are virtually absent in mature thymocytes. These results suggest how sialylation in a discrete segment of the CD8β stalk by ST3Gal-1 sialyltransferase creates a molecular developmental switch that affects ligand binding.