Review Interactions of protein antigens with antibodies

There are now several crystal structures of antibody Fab fragments complexed to their protein antigens. These include Fab complexes with lysozyme, two Fab complexes with influenza virus neuraminidase, and three Fab complexes with their anti-idiotype Fabs. The pattern of binding that emerges is similar to that found with other proteinprotein interactions, with good shape complementarity between the interacting surfaces and reasonable juxtapositions of polar residues so as to permit hydrogenbond formation. Water molecules have been observed in cavities within the interface and on the periphery, where they often form bridging hydrogen bonds between antibody and antigen. For the most part the antigen is bound in the middle of the antibody combining site with most of the six complementarity-determining residues involved in binding. For the most studied antigen, lysozyme, the epitopes for four antibodies occupy -45% of the accessible surface area. Some conformational changes have been observed to accompany binding in both the antibody and the antigen, although most of the information on conformational change in the latter comes from studies of complexes with small antigens. There has been a dramatic increase over the last 5 years in the number of Fab structures that have been determined by x-ray diffraction. It has been estimated that there are now >50 structures known to a resolution of between 3.0 and 2.0 A, although the coordinates of many of these are not yet available in the Protein Data Bank (Chemistry Department, Brookhaven National Laboratory, Upton, NY). By contrast, the structures of Fab complexes with protein antigens, the subject of this review, have risen more slowly and have been restricted to a small group of antigens, notably hen egg white lysozyme (HEL) and influenza virus neuraminidase. There have been a number of recent reviews of antibody structure and antibody-antigen associations (1-11). Braden and Poljak (11) in a recent review pay particular attention to the water molecules that surround the antibody-antigen interface and how these might influence the specificity. Whereas many of the general principles of these interactions, such as the shape complementarity of the interacting surfaces, are now well established, the increasing data base, including the examination of complexes with mutant antibody or antigen, the calorimetric analyses of binding, and the application of new techniques to epitope mapping, add increasing detail to this picture. In this brief review, we shall describe the structures that are now available and discuss the results in terms of the mechanism of antibody-antigen recognition and binding. Structures of Complexes with Protein