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 Galbeta1-3GlcNAc (Le(C)) related glycans, especially 3'-O-Su-Le(C), and towards 4'-O-sulfated lactosamine. Relatively high and uniform Ab binding to GalNAcalpha1-3Gal disaccharide demonstrated absence of correlation with fucosylated blood group A GalNAcalpha1-3(Fucalpha1-2)Gal antigen-similarly to well known relationship between Galalpha1-3Gal and true, fucosylated blood group B Galalpha1-3(Fucalpha1-2)Gal antigen. The binding intensity to Galalpha1-3Galbeta1-4GlcNAc 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 (-Galbeta1-4Glc) and glycoproteins (-GalNAcalpha) as a fragment of bigger glycans.
Huflejt
Margaret E
ME
New York University School of Medicine, Dept. of Cardiothoracic Surgery, New York, NY 10016, USA.
Vuskovic
Marko
M
Vasiliu
Daniela
D
Xu
Hongyu
H
Obukhova
Polina
P
Shilova
Nadezhda
N
Tuzikov
Alexander
A
Galanina
Oxana
O
Arun
Banu
B
Lu
Karen
K
Bovin
Nicolai
N
D000017:ABO Blood-Group System / Q000276:immunology; D000368:Aged; D000906:Antibodies / Q000097:blood*; D005260:Female; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000276:immunology; D046228:Microarray Analysis; D008875:Middle Aged; D011134:Polysaccharides / Q000276:immunology*
D000017:ABO Blood-Group System; D000906:Antibodies; D007983:Lewis Blood Group Antigens; D011134:Polysaccharides