{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Arata-Kawai H"],"funding":["NCI NIH HHS","NIGMS NIH HHS"],"pagination":["423-33"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3070580"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["178(1)"],"pubmed_abstract":["L-selectin initiates lymphocyte interactions with high endothelial venules (HEVs) of lymphoid organs through binding to ligands with specific glycosylation modifications. 6-Sulfo sLe(x), a sulfated carbohydrate determinant for L-selectin, is carried on core 2 and extended core 1 O-glycans of HEV-expressed glycoproteins. The MECA-79 monoclonal antibody recognizes sulfated extended core 1 O-glycans and partially blocks lymphocyte-HEV interactions in lymphoid organs. Recent evidence has identified the contribution of 6-sulfo sLe(x) carried on N-glycans to lymphocyte homing in mice. Here, we characterize CL40, a novel IgG monoclonal antibody. CL40 equaled or surpassed MECA-79 as a histochemical staining reagent for HEVs and HEV-like vessels in mouse and human. Using synthetic carbohydrates, we found that CL40 bound to 6-sulfo sLe(x) structures, on both core 2 and extended core 1 structures, with an absolute dependency on 6-O-sulfation. Using transfected CHO cells and gene-targeted mice, we observed that CL40 bound its epitope on both N-glycans and O-glycans. Consistent with its broader glycan-binding, CL40 was superior to MECA-79 in blocking lymphocyte-HEV interactions in both wild-type mice and mice deficient in forming O-glycans. This superiority was more marked in human, as CL40 completely blocked lymphocyte binding to tonsillar HEVs, whereas MECA-79 inhibited only 60%. These findings extend the evidence for the importance of N-glycans in lymphocyte homing in mouse and indicate that this dependency also applies to human lymphoid organs."],"journal":["The American journal of pathology"],"pubmed_title":["Functional contributions of N- and O-glycans to L-selectin ligands in murine and human lymphoid organs."],"pmcid":["PMC3070580"],"funding_grant_id":["R01 GM057411","R01 CA033000","R01 GM023547","P01- CA71932","P01 CA071932","R01-GM57411","R01-GM23547","R01-CA33000"],"pubmed_authors":["Zante Av","Rosen SD","Fukuda M","Wang YQ","Hemmerich S","Singer MS","Ito Y","Arata-Kawai H","Bao X","Bistrup A"],"additional_accession":[]},"is_claimable":false,"name":"Functional contributions of N- and O-glycans to L-selectin ligands in murine and human lymphoid organs.","description":"L-selectin initiates lymphocyte interactions with high endothelial venules (HEVs) of lymphoid organs through binding to ligands with specific glycosylation modifications. 6-Sulfo sLe(x), a sulfated carbohydrate determinant for L-selectin, is carried on core 2 and extended core 1 O-glycans of HEV-expressed glycoproteins. The MECA-79 monoclonal antibody recognizes sulfated extended core 1 O-glycans and partially blocks lymphocyte-HEV interactions in lymphoid organs. Recent evidence has identified the contribution of 6-sulfo sLe(x) carried on N-glycans to lymphocyte homing in mice. Here, we characterize CL40, a novel IgG monoclonal antibody. CL40 equaled or surpassed MECA-79 as a histochemical staining reagent for HEVs and HEV-like vessels in mouse and human. Using synthetic carbohydrates, we found that CL40 bound to 6-sulfo sLe(x) structures, on both core 2 and extended core 1 structures, with an absolute dependency on 6-O-sulfation. Using transfected CHO cells and gene-targeted mice, we observed that CL40 bound its epitope on both N-glycans and O-glycans. Consistent with its broader glycan-binding, CL40 was superior to MECA-79 in blocking lymphocyte-HEV interactions in both wild-type mice and mice deficient in forming O-glycans. This superiority was more marked in human, as CL40 completely blocked lymphocyte binding to tonsillar HEVs, whereas MECA-79 inhibited only 60%. These findings extend the evidence for the importance of N-glycans in lymphocyte homing in mouse and indicate that this dependency also applies to human lymphoid organs.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Jan","modification":"2021-02-25T08:37:26Z","creation":"2019-03-27T00:40:21Z"},"accession":"S-EPMC3070580","cross_references":{"pubmed":["21224079"],"doi":["10.1016/j.ajpath.2010.11.009"]}}