title: Sialic acid capping of CD8beta core 1-O-glycans controls thymocyte-major histocompatibility complex class I interaction.
abstract: Bidentate interaction of a T-cell receptor and CD8alphabeta heterodimer with a peptide-MHCI complex is required for the generation of cytotoxic T-lymphocytes. During thymic development, the modification of CD8beta 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 CD8beta-glycopeptides during T-cell development. Several threonine residues proximal to the CD8beta 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 CD8beta stalk by ST3Gal-1 sialyltransferase creates a molecular developmental switch that affects ligand binding.
authors.affiliation: Laboratory of Immunobiology, Department of Cancer Immunology & AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Moody
authors.forename: Simon J
authors.initials: SJ
authors.lastname: North
authors.forename: Bruce
authors.initials: B
authors.lastname: Reinhold
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Van Dyken
authors.forename: Mark E
authors.initials: ME
authors.lastname: Rogers
authors.forename: Maria
authors.initials: M
authors.lastname: Panico
authors.forename: Anne
authors.initials: A
authors.lastname: Dell
authors.forename: Howard R
authors.initials: HR
authors.lastname: Morris
authors.forename: Jamey D
authors.initials: JD
authors.lastname: Marth
authors.forename: Ellis L
authors.initials: EL
authors.lastname: Reinherz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis / Q000737:chemistry*; D015180:Electrophoresis, Gel, Two-Dimensional; D006020:Glycopeptides / Q000737:chemistry; D006031:Glycosylation; D008024:Ligands; D008285:Major Histocompatibility Complex; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*; D011485:Protein Binding; D012799:Sialyltransferases / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D006020:Glycopeptides; D008024:Ligands; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase