Antibody-antigen complexes contacts

At their most elaborate, epitope mapping techniques can provide detailed information on the amino acid residues in a protein antigen, which are in direct contact with the antibody binding site. X-ray crystallography of antibody-antigen complexes can identify contact residues directly and unequivocally, though not surprisingly in view of the effort required, this method is not in routine use. At the other extreme, demonstration by competition enzyme-linked immunosorbent assay (ELISA) methods that two antibodies bind to different sites on... 

Fig. 6. Water at protein-protein interfaces. Four protein-protein complexes are shown with one component in front of the other and the protein backbones drawn as a tube. The gray surface belongs to the back protein and is in contact with the front protein. Red spheres represent interface water molecules. The chymotrypsin-ovomu-coid (Icho) complex has a dry protease—inhibitor interface. The interface between the Fv fragments of antibodies D1.3 and E5.2 is a wet antibody—antigen complex (Idvf). These two interfaces are standard size, whereas the P-lactamase-BLIP inhibitor interface and the Ga-Gp interface of transducin (Igot) are large interfaces. Figure taken from Lo Conte et al. (1999) and drawn with GRASP (see Web Sites).

TABLE 10.5 Changes in surface areas and contacts in antibody-antigen complexes ... 

Type III reactions are caused by tissue injury due to immune complexes. The antigen-antibody complexes are usually cleared by the immune system however, repeated contact with antigens can cause the complex to deposit in tissue and result in tissue injury. Serum sickness is the classic example of a Type III reaction. Medications associated with serum sickness include many antibiotics, phenytoin, salicylates, barbiturates, nonsteroidal antiinflammatory drugs, isoniazid, antisera, hydralazine, captopril, and sulfonamides. Procainamide-induced lupus, described in Chapter 16, is also considered a Type III reaction. 

The challenge of how to represent the receptor that is deduced from these results is greatly helped by the use of computer graphics systems. For example, it was used to show the complementarity of molecular surfaces in the crystal structure of the complex between an antibody and lysozyme. The contact area is about 20x20 A. Side chains from one, such as Gin 121 of lysozyme, fit in a depression on the surface of the other protein. Interactions with small antigens, such as phosphorylcholine, have also demonstrated the specificity of the interactions between antibodies and antigens. 

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