Anti-carbohydrate antibodies of normal sera: Findings, surprises and challenges

We have used microchip format glycan array to characterize the individual carbohydrate recognition patterns by antibodies (Ab) in sera of 106 healthy donors. The glycan library included blood group antigens and other most frequent terminal oligosaccharides and their cores of mammalian N- and O-linked glycoproteins and glycolipids, tumor-associated carbohydrate antigens, and common components of bacterial/pathogenic polysaccharides and lipopolysaccharides, totally 205 glycans. The serum Ab interacted with at least 50 normal human glyco-motifs. Apart from expected blood group-, xeno- (heterophil) and infection-related binding activities, we observed a number of new and unexpected features. The surprising, relatively high antibody binding was found to the blood group P-1 and P-k trisaccharides and H(type 2) trisaccharide. Novel and very high binding activities have been observed towards Gal beta 1-3GlcNAc (Le(C)) related glycans, especially 3'-O-Su-Le(C), and towards 4'-O-sulfated lactosamine. Relatively high and uniform Ab binding to GalNAc alpha 1-3Gal disaccharide demonstrated absence of correlation with fucosylated blood group A GalNAc alpha 1-3(Fuc alpha 1-2)Gal antigen-similarly to well known relationship between Gal alpha 1-3Gal and true, fucosylated blood group B Gal alpha 1-3(Fuc alpha 1-2)Ga1 antigen. The binding intensity to Gal alpha 1 -3Gal beta 1-4GlcNAc xenoantigen was shown to be rather modest. Absence or very low Ab binding was found against oligosialic acid, sialooligosaccharides except SiaT(n), type 2 backbone glycans such as Le(y), and biantennary N-chain as well as its truncated forms, i.e. without terminal Sia, SiaGal, and SiaGalGlcNAc motifs. We have also found that Ab are capable of recognizing the short inner core typical for glycolipids (-Gal beta 1 -4Glc) and glycoproteins (-GalNAc alpha) as a fragment of bigger glycams. (C) 2009 Elsevier Ltd. All rights reserved.