A view of antibody maturation

Using X-ray crystallographic snapshots of antibodies with increasing affinities for a protein antigen, Yili Li, Roy Mariuzza (University of Maryland Biotechnology Institute, Rockville, MD), and colleagues suggest that protein–protein interactions are optimized by increasing hydrophobic stickiness and improving the fit between proteins.

Protein interactions are optimized by evolutionary changes that enhance the binding energy between the relevant molecules. The immune response offers a unique opportunity to study these changes in a practical time span. During affinity maturation, B cells produce antibodies with increasing affinity for the antigen—a sort of rapid molecular evolution resulting from somatic mutation of the antibody genes. Mariuzza's group examined the structural differences between four antibodies against a lysozyme antigen to determine how the antibodies improved their antigen-binding abilities.

They...