Developmentally regulated glycosylation of the CD8alphabeta 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 CD8alphabeta 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 CD8beta on mature thymocytes decreases CD8alphabeta-MHCI avidity by altering CD8alphabeta domain-domain association and/or orientation. Hence, glycans on the CD8beta stalk appear to modulate the ability of the distal binding surface of the dimeric CD8 globular head domains to clamp MHCI.
Moody
A M
AM
Laboratory of Immunobiology, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Chui
D
D
Reche
P A
PA
Priatel
J J
JJ
Marth
J D
JD
Reinherz
E L
EL
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D017637:Clonal Deletion / Q000502:physiology; D004268:DNA-Binding Proteins; D019281:Dimerization; D015329:Gene Rearrangement, T-Lymphocyte; D006031:Glycosylation; D006183:H-2 Antigens / Q000737:chemistry / Q000276:immunology; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000502:physiology; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012799:Sialyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000166:cytology*; D019076:Transgenes; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D016827:CD8 Antigens; C433839:CD8alphabeta antigen; D004268:DNA-Binding Proteins; D006183:H-2 Antigens; D008024:Ligands; D011134:Polysaccharides; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; C064655:V(D)J recombination activating protein 2; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase