A monoclonal antibody to Lewis Y/Lewis b revealing mimicry of the histone H1 to carbohydrate structures.
Antibodies to either peptide or carbohydrate tumour antigens are established tools for diagnostics and therapy. We here describe an antibody (A70-A/A9) recognizing a carbohydrate epitope common to the tumour-associated Lewis Y and Lewis b antigens (Fucalpha1-2Galbeta1-4/3[Fucalpha1-3/4]GlcNAcbeta-). Its specificity was established without doubt with a panel of 86 synthetic mono- and oligosaccharidic structures. This antibody was found to cross-react with the nuclear protein histone H1. Binding to H1 was specific, periodate-insensitive (non-carbohydrate) and saturable. Histone H1 was able to inhibit Lewis Y binding very effectively in a concentration-dependent manner. We conclude that it represents an example of natural peptide mimicry of a carbohydrate epitope. It may explain the observed occurrence of 'anti-histone autoantibodies' in cancer patients.
Christensen
P A
PA
Glycotope GmbH, Robert-Rössle-Str. 10, Berlin-Buch, Germany.
Danielczyk
A
A
Ravn
P
P
Stahn
R
R
Karsten
U
U
Goletz
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D015153:Blotting, Western; D002241:Carbohydrates / Q000276:immunology*; D003429:Cross Reactions; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D006657:Histones / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D051379:Mice; D018716:Molecular Mimicry; D009844:Oligosaccharides / Q000276:immunology*; D020349:Surface Plasmon Resonance
C500822:3-aminopropyl fucopyranosyl-1-2-galactopyranosyl-1-3-(fucopyranosyl-1-4)-2-acetamido-2-deoxyglucopyranosyl-1-3-galactopyranosyl-1-4-glucopyranoside; D000911:Antibodies, Monoclonal; D002241:Carbohydrates; D018985:Epitopes, B-Lymphocyte; D006657:Histones; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D009844:Oligosaccharides