Background: Antibody binding to xenobiotic ␣-Gal structures mediates anaphylaxis. Results: Humanized IgE antibodies exhibit recognition footprints similar to serum immunoglobulins but have no capability of effector cell activation. Conclusion: Recognition of the ␣-Gal epitope is based on the terminal disaccharide, but interaction does not imply cellular activation. Significance: These data provide the first insights into the recognition of carbohydrate IgE epitopes.