Sialic acid capping of CD8beta core 1-O-glycans controls thymocyte-major histocompatibility complex class I interaction

J Biol Chem. 2003 Feb 28;278(9):7240-6. doi: 10.1074/jbc.M210468200. Epub 2002 Nov 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4 Antigens / biosynthesis
  • CD8 Antigens / biosynthesis
  • CD8 Antigens / chemistry*
  • Electrophoresis, Gel, Two-Dimensional
  • Glycopeptides / chemistry
  • Glycosylation
  • Ligands
  • Major Histocompatibility Complex*
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Molecular Sequence Data
  • N-Acetylneuraminic Acid / chemistry*
  • Protein Binding
  • Sialyltransferases / metabolism
  • Thymus Gland / cytology*

Substances

  • CD4 Antigens
  • CD8 Antigens
  • Glycopeptides
  • Ligands
  • Sialyltransferases
  • beta-galactoside alpha-2,3-sialyltransferase
  • N-Acetylneuraminic Acid