Antibody Recognition of the Blood Group A Oligosaccharide Antigen. Sonia I. Patenaude*, Rebecca J. To+, Doris Bilous+, N. Martin Young+ and Stephen V. Evans*. *Department of Biochemistry, University of Ottawa, Ottawa K1H 8M5, Canada. +Institute for Biological Sciences, National Research Council of Canada, Ottawa K1A 0R6, Canada.

A single-chain Fv antigen-binding fragment of an antibody specific for the blood group A oligosaccharide antigen has been expressed from a synthetic gene construct, crystallized, and its three-dimensional structure determined to 2.2 Å resolution. The surface of the Fv shows a deep pocket that acts to distinguish between the blood group A and B antigens, which differ only in the presence of an N-acetyl group on the terminal galactose residue. Remarkably, the second hypervariable loop corresponding to the antibody heavy chain displays two distinct conformations. This suggests that the formation of the antigen-Fv complex would require significant conformational rearrangement. The structures of anti-carbohydrate antibodies usually display minimum conformational flexibility, which has been attributed partly to the entropic penalty that they would experience upon the formation of a rigid antigen-antibody complex. The present structure suggests that an antibody can display some degree of flexibility in its antigen-binding site with a minimum entropic penalty by utilizing hypervariable loops that possess a small number of stable conformations.