Glycosylation of immunoglobulin A influences its receptor binding.
Immunoglobulin A (IgA), which is heavily glycosylated, interacts with a variety of receptors, e.g. the asialoglycoprotein receptor (ASGP-R), which binds terminal galactose residues, and the Fcalpha receptor (FcalphaRI). It has thus been proposed that elevated serum levels of IgA in primary Sjögren's syndrome (pSS) are caused by its defective clearance. To test this hypothesis, we developed a method (based on sialyl transferases eluted from a hepatoma cell line) to increase the amount of sialic acid (SA) on IgA, and used a battery of IgA1- and IgA2-specific glycosidases to reduce this amount. Binding of IgA1 and IgA2 to ASGP-R and FcalphaRI was found to be sugar dependent because oversialylated IgA bound less than native or desialylated IgA. However, individual sugars did not play a direct role in this binding. Given that IgA are oversialylated in pSS, defective clearance of IgA may indeed be ascribed to an excess of SA in IgA1 and IgA2.
Basset
C
C
Brest University Medical School, Brest, France.
Devauchelle
V
V
Durand
V
V
Jamin
C
C
Pennec
Y L
YL
Youinou
P
P
Dueymes
M
M
D000116:Acetylgalactosamine / Q000494:pharmacology; D000117:Acetylglucosamine / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology; D004705:Endocytosis; D005690:Galactose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry* / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology; D019158:N-Acetylneuraminic Acid / Q000032:analysis; D009363:Neoplasm Proteins / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D011961:Receptors, Fc / Q000378:metabolism*; D012799:Sialyltransferases / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000276:immunology; D014407:Tumor Cells, Cultured; D020298:U937 Cells
C045281:IgA receptor; D007070:Immunoglobulin A; D009363:Neoplasm Proteins; D011961:Receptors, Fc; D012799:Sialyltransferases; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D005947:Glucose; D000116:Acetylgalactosamine; D000117:Acetylglucosamine; D005690:Galactose