Details

Autor(en) / Beteiligte

• Ramsland, Paul A
• Farrugia, William
• Bradford, Tessa M
• Mark Hogarth, P
• Scott, Andrew M

Titel

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

Ist Teil von

• Journal of molecular biology, 2004-07, Vol.340 (4), p.809-818

Ort / Verlag

England

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• Antibodies targeting human epithelial carcinomas bearing Lewis Y (Le(y)) carbohydrate antigens provide a striking illustration of convergent immune recognition. We report a 1.9A resolution crystal structure of the Fab of a humanized antibody (hu3S193) in complex with the Le(y) tetrasaccharide, Fuc(alpha 1-->2)Gal(beta 1-->4)[Fuc(alpha 1-->3)]GlcNAc. Comparisons of the hu3S193 and BR96 antibodies bound to Le(y) tumor antigens revealed extremely similar mechanisms for recognition of the carbohydrate epitopes. Solvent plays a critical role in hu3S193 antibody binding to the Le(y) carbohydrate epitope. Specificity for Le(y) is maintained because a conserved pocket accepts an N-acetyl group of the core Gal(beta 1-->4)GlcNAc disaccharide. Closely related blood-group determinants (Le(a) and Le(b)) cannot enter the specificity pocket, making the Le(y) antibodies promising candidates for immunotherapy of epithelial cancer.