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.