Structural convergence of antibody binding of carbohydrate determinants in Lewis Y tumor antigens.
J Mol Biol
; 340(4): 809-18, 2004 Jul 16.
Article
em En
| MEDLINE
| ID: mdl-15223322
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.
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Base de dados:
MEDLINE
Assunto principal:
Carboidratos
/
Antígenos Glicosídicos Associados a Tumores
/
Antígenos do Grupo Sanguíneo de Lewis
/
Anticorpos Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article