Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment

Mitoma, Junya; Bao, Xingfeng; Petryanik, Bronislawa; Schaerli, Patrick; Gauguet, Jean Marc; Yu, Shin‐Yi; Kawashima, Hiroto; Saitō, Hideo; Ohtsubo, Kazuaki; Marth, Jamey D.; Khoo, Kay‐Hooi; Andrian, Ulrich H. von; Lowe, John B.; Fukuda, Minoru

doi:10.1038/ni1442

Cited by 168 publications

(142 citation statements)

References 52 publications

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“…The lymphocyte homing to PLNs in C1␤3GnT and C2GnT-I DKO mice was diminished by ϳ60% compared with that in WT mice in our assay (Fig. 9A), consistent with previous findings (8), confirming that O-glycans are important for lymphocyte homing to PLNs. To determine the importance of sulfated N-glycans in lymphocyte homing, we next examined whether S2 could inhibit the FIGURE 7.…”

Section: S2 Significantly Inhibited the N-glycan-dependent Lymphocytesupporting

confidence: 81%

“…Consistent with the results of the glycan array, S1 and S2 bound well to HEVs of the PLNs from FucT-IV and FucT-VII DKO mice (6). As expected, MECA-79 bound to the HEVs of fucosyltransferase DKO mice, whereas it failed to bind the HEVs of C1␤3GnT and C2GnT-I DKO mice, which lack sulfated O-glycans (8). To our surprise, binding of S1 to the HEVs of C1␤3GnT and C2GnT-I DKO mice was almost completely abolished compared with its binding to the HEVs of WT mice.…”

Section: S1 Preferentially Bound Sulfated O-glycans Whereas S2 Boundsupporting

confidence: 74%

“…Ϫ/Ϫ C2GnT-I Ϫ/Ϫ mice were backcrossed at least five generations to C57BL/6 WT mice and maintained as described previously (6,8,9). C57BL/6 WT and BALB/c Slcnu/nu mice were purchased from Japan SLC (Hamamatsu, Japan).…”

Section: And C1␤3gntmentioning

confidence: 99%

“…Studies with mice deficient in core 1 ␤1,3-N-acetylglucosaminyltransferase (C1␤3GnT) and core 2 ␤1,6-N-acetylglucosaminyltransferase-I (C2GnT-I), which are involved in the biosynthesis of the O-glycan core structures required for the modification with 6-sulfo sialyl Lewis X (supplemental Fig. S1), showed that both N-and O-glycans are important in lymphocyte homing and recruitment (8). However, it was not shown in those studies that sulfated N-glycans could indeed mediate lymphocyte homing, because specific probes against sulfated N-glycans were not available.…”

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confidence: 99%

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Novel Anti-carbohydrate Antibodies Reveal the Cooperative Function of Sulfated N- and O-Glycans in Lymphocyte Homing

Hirakawa

Tsuboi

Sato

et al. 2010

Journal of Biological Chemistry

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Cell surface glycans play pivotal roles in immune cell trafficking and immunity. Here we present an efficient method for generating anti-carbohydrate monoclonal antibodies (mAbs) using gene-targeted mice and describe critical glycans in lymphocyte homing. We immunized sulfotransferase GlcNAc6ST-1 and GlcNAc6ST-2 doubly deficient mice with sulfotransferase-overexpressing Chinese hamster ovary cells and generated two mAbs, termed S1 and S2. Both S1 and S2 bound high endothelial venules (HEVs) in the lymphoid organs of humans and wild-type mice, but not in those of doubly deficient mice. Glycan array analysis indicated that both S1 and S2 specifically bound 6-sulfo sialyl Lewis X and its defucosylated structure. Interestingly, S2 inhibited lymphocyte homing to peripheral lymph nodes by 95%, whereas S1 inhibited it by only 25%. S2 also significantly inhibited contact hypersensitivity responses and L-selectin-dependent leukocyte adhesion to HEVs. Immunohistochemical and Western blot analyses indicated that S1 preferentially bound sulfated O-glycans, whereas S2 bound both sulfated N-and O-glycans in HEVs. Furthermore, S2 strongly inhibited the N-glycan-dependent residual lymphocyte homing in mutant mice lacking sulfated O-glycans, indicating the importance of both sulfated N-and O-glycans in lymphocyte homing. Thus, the two mAbs generated by a novel method revealed the cooperative function of sulfated N-and O-glycans in lymphocyte homing and immune surveillance.

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Section: S2 Significantly Inhibited the N-glycan-dependent Lymphocytesupporting

confidence: 81%

Section: S1 Preferentially Bound Sulfated O-glycans Whereas S2 Boundsupporting

confidence: 74%

Section: And C1␤3gntmentioning

confidence: 99%

mentioning

confidence: 99%

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Novel Anti-carbohydrate Antibodies Reveal the Cooperative Function of Sulfated N- and O-Glycans in Lymphocyte Homing

Hirakawa

Tsuboi

Sato

et al. 2010

Journal of Biological Chemistry

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“…Borates were then removed by repeated co-evaporation with 10% acetic acid in methanol under a stream of nitrogen. An aliquot of the released and desalted O-glycans was permethylated and analyzed by MALDI-MS and MS/MS on a 4700 Proteomics Analyzer (Applied Biosystem, Farmington, MA) as described previously (32,33).…”

Section: Experimental and Proceduresmentioning

confidence: 99%

Core3 O-Glycan Synthase Suppresses Tumor Formation and Metastasis of Prostate Carcinoma PC3 and LNCaP Cells through Down-regulation of α2β1 Integrin Complex

Lee

Hatakeyama

et al. 2009

Journal of Biological Chemistry

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Cancer cells often express surface carbohydrates different from normal cells (1). One such change is expression of sialyl Lewis X and Lewis B blood group antigens in cancer cells (2, 3). These structural elements are seen as capping oligosaccharides attached to the underlying glycan backbone where they likely function as ligands for cell adhesion molecules.The structure of underlying glycans also changes during malignant transformation and differentiation. In particular, there are several reports that an increase in the ␤1,6-N-acetylglucosaminyl branch in N-glycans synthesized by ␤1,6-Nacetylglucosaminyltransferase-V is associated with oncogenic transformation (4 -7). Similar structural changes are seen in mucin-type O-glycans, which have N-acetylgalactosamine at the reducing end linked to polypeptide threonine or serine residues. Addition of different carbohydrate residues to N-acetylgalactosamine confers a variety of backbone structures on mucin-type O-glycans; the most abundant of those are classified as core1, core2, core3, and core4 O-glycans (8) (Fig.

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Development and Use of IgM/J‐Chain Fusion Proteins for Characterization of Immunoglobulin Superfamily Ligand‐Receptor Interactions

Ammann

Trowsdale

2014

CP Protein Science

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Discovery of binding partners for immunoglobulin molecules expressed by cells of the immune system is an important topic of current research. However, many ligand-receptor interactions are of low affinity, and hence detection is refractory to most established protocols. We evaluated fusion proteins based on human IgM as high avidity probes to screen for ligand-receptor binding. We describe methods for cloning, expression, and quantification of IgM fusion proteins with J-chain. Furthermore, we outline protocols to assess binding of IgM fusion proteins to cells and to plate-bound proteins. Compared to standard IgG-fusion proteins, IgM + J chain increased binding of a test interaction, PD-L1 to PD-1, up to 1000-fold.

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Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment

Cited by 168 publications

References 52 publications

Novel Anti-carbohydrate Antibodies Reveal the Cooperative Function of Sulfated N- and O-Glycans in Lymphocyte Homing

Novel Anti-carbohydrate Antibodies Reveal the Cooperative Function of Sulfated N- and O-Glycans in Lymphocyte Homing

Core3 O-Glycan Synthase Suppresses Tumor Formation and Metastasis of Prostate Carcinoma PC3 and LNCaP Cells through Down-regulation of α2β1 Integrin Complex

Development and Use of IgM/J‐Chain Fusion Proteins for Characterization of Immunoglobulin Superfamily Ligand‐Receptor Interactions

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