Human T cell IgD receptors react with O-glycans on both human IgD and IgA1

Abstract

Previous studies on murine T cell IgD-R have shown that these receptors recognize N-glycans of murine IgD, and not of other Ig isotypes. We have now studied the specificity of IgD-R on human T cells. Human IgD digested with proteinase K to fragments of X 5 kDa inhibit the ability of T cells to form rosettes with IgD-coated ox erythrocytes. The same amount of digested IgG does not. We tested all the human Ig isotypes: IgG1,-2,-3,-4, IgA2, IgE and IgM fail to inhibit significantly at 20 ? g/assay. However, IgA1 is as effective as IgD itself, showing approximately 60 % and 80 % inhibition at 5 ? g and 10 ? g/assay. Human IgA1 and IgD both contain Gal-1 1 3-GalNac-rich O-linked glycans, and on this basis are both bound to ricin and jacalin. The O-linked glycans may therefore also represent the common moiety binding to IgD-R. Disaccharides Gal-1 1 3-GalNac, and Gal-1 1 4-Glc at 10 ? g/assay blocked IgD rosetting while Gal-1 1 6-Glc did not. We conclude that the human IgD-R is a lectin, differing from the murine IgD-R in that it has both IgA1 and IgD as ligands.

Discovery and Characterization of Secretory IgD in Rainbow Trout: Secretory IgD Is Produced through a Novel Splicing Mechanism

“…Recently, it was hypothesized that these variants may increase IgD diversity to compensate for the lack of class switch recombination in fish (24). Alternatively, in mammals it has been demonstrated that the carbohydrates found on IgD may facilitate specific receptor binding to T cells (27,28) or granulocytic cells (17). Thus, the two splice variants characterized in this study, which contain different numbers of N-linked glycosylation sites, may facilitate different effector functions in trout.…”

The Tn Antigen—Structural Simplicity and Biological Complexity

“…Glycoproteins containing core 1 or 2 O ‐glycans include the low‐density‐lipoprotein (LDL) receptor,136–138 the transferrin receptor,129, 139–141 glycophorin A,142–144 podoplanin,145–147 PSGL‐1,30, 148–150 CD34,151 endoglycan,152 zona pellucida glycoprotein ZP3,153, 154 CD43,155–157 CD45,158–161 the TRAIL receptor family,162 the neurotrophin receptor,163, 164 the MUC family of mucins (both membrane‐bound and secreted),165–169 platelet glycoprotein GPIbα,170 and platelet integrin GPIIb/IIIa (αIIbβ3) 171. Such core 1 and/or 2 O ‐glycans are also found in many secreted and serum glycoproteins, including human IgA1172–177 and IgD,178–180 erythropoietin,181–184 von Willebrand factor (vWF),185 blood coagulation factor X,186 serum apoC‐III,187–189 human chorionic gonadotropin (HCG),190–193 interleukin‐6 (IL‐6),194, 195 Tamm–Horsfall glycoprotein/uromodulin,196–199 Gc macrophage activating factor (GcMAF, a naturally derived form of human vitamin D binding protein),200 human urinary thrombomodulin,201 and human milk bile‐salt‐stimulated lipase 202–205. Furthermore, O ‐glycans are found in virtually all mucin secretions of epithelial cells and on the surface of all animal cells, including erythrocytes.…”

IgA receptors in health and disease

“…T cells, however, did not rosette IgA1‐coated erythrocytes. The binding of IgD is calcium dependent and binding of IgD and IgA1 occurs via the O ‐linked carbohydrates unique to the hinge regions of these antibodies (78, 79). The O ‐linked glycans on the IgD and IgA1 hinge are frequently Gal1→3GalNac, and incubation with this disaccharide inhibited IgD‐dependent rosetting (79).…”

“…The binding of IgD is calcium dependent and binding of IgD and IgA1 occurs via the O ‐linked carbohydrates unique to the hinge regions of these antibodies (78, 79). The O ‐linked glycans on the IgD and IgA1 hinge are frequently Gal1→3GalNac, and incubation with this disaccharide inhibited IgD‐dependent rosetting (79). The recent report (58) of galectin 1 binding to glycans in the hinge of IgA1 may indicate that galectin 1 could be responsible for IgA1/IgD binding to T cells.…”