HB4 antibody recognizes a carbohydrate structure on lymphocyte surface proteins related to HB6, CDw75, and CD76 antigens.
Cells regulate the specificity of the carbohydrate chains on their membrane-bound glycoconjugates by differential expression of glycosyltransferases. In lymphocytes, beta-galactoside alpha 2,6-sialyltransferase is reportedly involved in the generation of epitopes recognized by HB6, CDw75, and CD76 mAb. The HB4 mAb binds to an Ag present on subpopulations of B and NK cells. We now show that this Ag represents another member of a set of neuraminidase-sensitive, alpha 2,6-sialyltransferase-generated sugar Ag. Transient expression of a cDNA encoding this enzyme in COS cells generated a minor population of HB4+ cells that was completely contained within the HB6+ COS cell population. Using various proteinases and an inhibitor of N-linked carbohydrate processing, we show both epitopes to represent components of N-glycosylated membrane proteins. Remarkably, porcine thyroglobulin, an alpha 2,6-NeuAc+ glycoprotein, is specifically recognized by both mAb. These data underline a close relationship between HB4 and HB6 epitopes and imply further that both mAb react with oligosaccharide chains irrespective of the carrier molecule nature. Thus, the terminal sugar residue sialic acid plays a pivotal role in at least four distinct epitopes that are expressed differentially in immune cells. This may point at an important role for these epitopes in biologic recognition.
Department of Immunology, University Hospital Utrecht, The Netherlands.
W B
WB
De Lau
J
J
Kuipers
H
H
Voshol
H
H
Clevers
B J
BJ
Bast
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D001666:Binding Sites, Antibody; D002460:Cell Line; D006001:Glycoconjugates / Q000276:immunology; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D009439:Neuraminidase / Q000276:immunology; D009844:Oligosaccharides / Q000276:immunology*; D012799:Sialyltransferases / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; C063411:CD76 antigen; D006001:Glycoconjugates; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; C072272:HB-6 antigen; D012799:Sialyltransferases; C093493:ST6GAL1 protein, human; D009439:Neuraminidase; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase