Sci. STKE, 20 November 2001
Glycosylation Regulated by Sialylation
As thymocytes mature, their cell-surface proteins change both in terms of which proteins are present and in the structure of the proteins present. Moody et al. investigated how changes in glycosylation of the CD8 cell-surface glycoprotein of thymocytes influence its interaction with major histocompatibility complex class I (MHCI) molecules. Peptide MHCI tetramers (pMHCIs) were used in combination with fluorescent cell sorting (FACS) analysis to show that immature thymocytes that are positive for both CD8 and CD4 (another cell-surface receptor), so-called "DP" thymocytes, interact with the pMHCIs. Mature thymocytes that only express CD8 or CD4 (so-called "SP" thymocytes) did not interact with the pMHCIs, despite the fact that the DP and CD8 SP thymocytes express the same amount of CD8α and β subunits. Biochemical analysis of CD8α and β from DP and SP thymocytes showed that the transition to SP led to a decrease in molecular heterogeneity of the β subunit and marked reduction in the ability of the β subunit to be affinity-purified by the lectin peanut agglutinin (PNA). Treatment of SP thymocytes with neuraminidase to remove sialic acid from O-glycans restored PNA and pMHCI binding, suggesting that sialylation of the β subunit is responsible for the change in MHCI binding capacity of the SP thymocytes. Analysis of pMHCI binding to thymocytes from a mouse lacking the sialyltransferase ST3Gal-1 gene showed that the SP thymoctyes bound pMHCIs and maintained a high PNA-binding character throughout maturation. The change in glycosylation and the resulting effect on MHC binding appear to influence CD8 thymic selection in that in 4 of 14 animals tested, the lack of the ST3 Gal-1 gene resulted in a decrease in the number of CD8-positive SP thymocytes.
A. M. Moody, D. Chui, P. A. Reche, J. J. Priatel, J. D. Marth, E. L. Reinherz, Developmentally regulated glycosylation of the CD8αβ coreceptor stalk modulates ligand binding. Cell 107, 501-512 (2001). [Online Journal]
Citation: Regulated by Sialylation. Sci. STKE 2001, tw429 (2001).
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