Publications & Reports

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

Ramsland PA, Farrugia W, Bradford TM, Mark Hogarth P, Scott AM
Structural Immunology Laboratory, Austin Research Institute, Heidelberg, Vic. 3084, Australia. p.ramsland@ari.unimelb.edu.au

Abstract

Antibodies targeting human epithelial carcinomas bearing Lewis Y (Le(y)) carbohydrate antigens provide a striking illustration of convergent immune recognition. We report a 1.9A 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.

Publication

  • Journal: Journal of Molecular Biology
  • Published: 16/07/2004
  • Volume: 340
  • Issue: 4
  • Pagination: 809-818

Author