The Chemistry and Mechanism of Antibody Binding to Protein Antigens

Abstract

There are already a number of authoritative reviews on protein immunogenicity. The chapter discuses the chemical nature of the recognition process associated with the production of antibodies. Detailed crystallographic information on the structure of antibody–antigen complexes is described in the chapter. Although there are many different ways to identify protein epitopes, the chapter focuses primarily on results from X-ray crystallography and peptide mapping, because these currently provide the most suitable data base for the consideration of the chemistry and mechanism of antibody binding to protein antigens. Most antibodies raised against intact proteins recognize conformational sites, consequently, do not bind peptides or proteolytic fragments with high affinity. Yet, some antibodies raised against native protein antigens do bind to peptide homologs of the protein sequence, allowing the chemistry of these sites to be probed at the resolution of single amino acid side chains. Some antibodies raised against the native protein appear to recognize the denatured forms of the protein only. Crystallographic approaches to characterize antibody–antigen complexes are limited by practical constraints, resulting from the experimental difficulties of protein crystallization and from the extensive time and equipment requirements. Nevertheless, the crystallographic structures of antibody complexes with protein antigens provide a wealth of information with which all other biochemical and immunological experiments must be reconciled.