Sulfated glycans directly interact with mouse Thy-1 and negatively regulate Thy-1-mediated adhesion of thymocytes to thymic epithelial cells.
Thy-1 is a major brain cell surface glycoprotein of adult mammal species also expressed in rodent thymus. Despite extensive studies, the function(s) of this molecule has remained so far ill defined. We have recently shown that Thy-1 was involved in the adhesion of mouse thymocytes to thymic epithelium through a specific interaction with a heterophilic ligand(s) expressed on the epithelial cell surface. In the present study, we aimed at evaluating the interaction of sulfated glycans with mouse Thy-1, as well as its consequence on Thy-1-mediated thymic lympho-epithelial cell interaction. It was shown that 125I-labeled Thy-1 directly bound to immobilized heparin. Sulfated glycans such as pentosan sulfate, dextran sulfate, and fucoidan were found to strongly inhibit the binding of Thy-1 to heparin. In contrast, chondroitin sulfate, keratan sulfate, and heparan sulfate were not inhibitory. Sulfated glycans (e.g., pentosan sulfate, assayed at a concentration of 50 micrograms/ml) completely blocked the Thy-1-dependent adhesion of T cells to a mouse thymic epithelial cell monolayer. To explore the mechanism of this inhibition, we compared the ability of T cell to adhere to mouse thymic epithelial cell monolayer or to sulfated glycans. Our results suggest that sulfated glycans bind to a Thy-1 site distinct from that with which this molecule interacts with its heterophilic ligand. Moreover, sulfate glycans could modulate the binding of rat mAb directed at spatially distinct Thy-1 epitopes. The present results identified a potential mechanism regulating Thy-1-mediated lympho-epithelial cell adhesion.
Hueber
A O
AO
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Pierres
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M
He
H T
HT
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D001667:Binding, Competitive; D002448:Cell Adhesion; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004847:Epithelial Cells; D000939:Epitopes; D006493:Heparin / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018800:Thy-1 Antigens; D013950:Thymus Gland / Q000166:cytology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens; D006493:Heparin; D002809:Chondroitin Sulfates