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

PA Ramsland, W Farrugia, TM Bradford… - Journal of molecular …, 2004 - Elsevier
Journal of molecular biology, 2004Elsevier
Antibodies targeting human epithelial carcinomas bearing Lewis Y (Ley) carbohydrate
antigens provide a striking illustration of convergent immune recognition. We report a 1.9 Å
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 …
Antibodies targeting human epithelial carcinomas bearing Lewis Y (Ley) 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 disaccharide. Closely related blood-group determinants (Lea and Leb) cannot enter the specificity pocket, making the Ley antibodies promising candidates for immunotherapy of epithelial cancer.
Elsevier