Early murine T-lymphocyte activation is accompanied by a switch from N-glycolyl- to N-acetyl-neuraminic acid and generation of ligands for siglec-E

Pierre Redelinghuys, Aristotelis Antonopoulos, Yan Liu, Maria A. Campanero-Rhodes, Emma McKenzie, Stuart M. Haslam, Anne Dell, Ten Feizi, Paul R. Crocker (Lead / Corresponding author)

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    30 Citations (Scopus)

    Abstract

    It is well established that murine T-lymphocyte activation is accompanied by major changes in cell-surface sialylation, potentially influencing interactions with sialic acid-binding immunoglobulin-like lectins (siglecs). In the present study, we analyzed early activation of murine CD4+ and CD8+ T-lymphocytes at 24 h. We observed a striking and selective up-regulation in the binding of a recombinant soluble form of siglec-E, an inhibitory siglec, which is expressed on several myeloid cell types including antigen-presenting dendritic cells. In contrast, much lower levels of T cell binding were observed with other siglecs, including sialoadhesin, CD22, and siglec-F and the plant lectins Maackia amurensis leukoagglutinin and Sambucus nigra agglutinin. By mass spectrometry, the sialic acid content of 24-h-activated CD4+ and CD8+ T-lymphocytes exhibited an increased proportion of N-acetyl-neuraminic acid (NeuAc) to N-glycolyl-neuraminic acid (NeuGc) in N-glycans. Reduced levels of NeuGc on the surface of activated T cells were demonstrated using an antibody specific for NeuGc and the expression levels of the gene encoding NeuAc-to NeuGc-converting enzyme, CMP-NeuAc hydroxylase, were also reduced. Siglec-E bound a wide range of sialylated structures in glycan arrays, had a preference for NeuAc versus NeuGc-terminated sequences and could recognize a set of sialoglycoproteins that included CD45, in lysates from activated T-lymphocytes. Collectively, these results show that early in T cell activation, glycan remodelling involves a switch from NeuGc- to NeuAc-terminating oligosaccharides on cell surface glycoproteins. This is associated with a strong up-regulation of siglec-E ligands, which may be important in promoting cellular interactions between early activated T-lymphocytes and myeloid cells expressing this inhibitory receptor.

    Original languageEnglish
    Pages (from-to)34522-34532
    Number of pages11
    JournalJournal of Biological Chemistry
    Volume286
    Issue number40
    Early online date11 Aug 2011
    DOIs
    Publication statusPublished - 7 Oct 2011

    Keywords

    • Tyrosine phosphatases SHP-1
    • O-glycan biosynthesis
    • Surface sialic acids
    • Immune system
    • Differential glycosylation
    • Neoglycolipid technology
    • Acetylneuraminic acid
    • Linked oligosaccharides
    • Human evolution
    • Cell death

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