Structural convergence of antibody binding of carbohydrate determinants in Lewis Y tumor antigens

Abstract

Antibodies targeting human epithelial carcinomas bearing Lewis Y (Le y) carbohydrate antigens provide a striking illustration of convergent immune recognition. We report a 1.9Å resolution crystal structure of the Fab of a humanized antibody (hu3S193) in complex with the Ley tetrasaccharide, Fuc(α1→2)Gal(β1→4) [Fuc(α1→3)]GlcNAc. Comparisons of the hu3S193 and BR96 antibodies bound to Ley tumor antigens revealed extremely similar mechanisms for recognition of the carbohydrate epitopes. Solvent plays a critical role in hu3S193 antibody binding to the Ley carbohydrate epitope. Specificity for Ley is maintained because a conserved pocket accepts an N-acetyl group of the core Gal(β1→4)GlcNAc disac..