Sialic acid capping of CD8beta core 1-O-glycans controls thymocyte-major histocompatibility complex class I interaction.
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.
Moody
Anne Marie
AM
Laboratory of Immunobiology, Department of Cancer Immunology & AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA.
North
Simon J
SJ
Reinhold
Bruce
B
Van Dyken
Steven J
SJ
Rogers
Mark E
ME
Panico
Maria
M
Dell
Anne
A
Morris
Howard R
HR
Marth
Jamey D
JD
Reinherz
Ellis L
EL
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
D015704:CD4 Antigens; D016827:CD8 Antigens; D006020:Glycopeptides; D008024:Ligands; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase