ANTIBODY-ANTIGEN INTERACTIONS

The structural origins of antibody diversity are well understood as a result of X-ray crystallographic and molecular modelling studies of Fab fragments. A similar understanding of antibody specificity is beginning to emerge from an analysis of structures of hapten, peptide and protein antibody complexes. While the nature of the antibody-antigen interface, and any conformational changes that occur on complex formation, can be described in structural terms, a full explanation of the thermodynamic and mechanistic basis of affinity is less accessible from structure alone. A number of physiochemical studies carried out on wild type and mutant antibodies have raised questions about the nature of the energetics of the interaction, and the possibility of a key role for water molecules has been discussed. The possibility of 'induced fit' as a common mechanism for antigen-antibody interactions has been raised, and a molecular basis for hapten and protein cross-reactivity proposed. These recent contributions to the field, as well as providing partial solutions to old problems, have provided exciting new insights.