Developmentally regulated glycosylation of the CD8alphabeta coreceptor stalk modulates ligand binding. |
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| Authors: | A M Moody D Chui P A Reche J J Priatel J D Marth E L Reinherz |
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| Institution: | Laboratory of Immunobiology, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. |
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| Abstract: | 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. |
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