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.