Chapter 6 The antigen-antibody complex: Structure and recognition

Summary The antigen binding site of antibodies is a chemically and structurally variable surface of amino acids located at the extremities of the arms of the -Y- shaped molecule. Six hypervariable loops (Complementarily Determining Regions) contribute to this surface and determine the specificity of the antibody. Three of these CDRs are on the V H domain and three are on the V L domain, and their relative positions in space are determined by the interactions at the V L -V H dimer interface. That interface has unusual architectural features when compared with the database of protein structures. Antibodies behave like other protein molecules when they associate with a ligand. They may change their structure, at the level either of the peptide backbone or side chain conformation, to achieve improved fit with the antigen. In addition, the V L and V H domains themselves may undergo some rearrangement across the V L -V H interface upon binding an antigen. The V L -V H interface plays the role of an adaptor, permitting movement of V L CDRS relative to V H CDRS SO that shape complementarity of the entire CDR surface to the antigen can be optimized. The diversity of CDR sequences, coupled with the ability to adopt a number of related conformations, results in a formidable armada of antibody specificities.