STRUCTURE OF AN ANTIIDIOTYPIC FAB AGAINST FELINE PERITONITIS VIRUS-NEUTRALIZING ANTIBODY AND A COMPARISON WITH THE COMPLEXED FAB

The crystal structure of anti-idiotopic Fab 409.5.3, made against an E 2 specific feline infectious peritonitis virus-neutralizing antibody 7 30.1.4, has been determined in its free form, at 2.9 Angstrom resoluti on by molecular replacement. This antibody, used as an immunogen, elic its the production of anti-anti-idiotypic antibodies that in turn neut ralize the virus. The structure of the uncomplexed Fab was refined usi ng constrained-restrained least squares minimization and simulated ann ealing in combination with conjugate gradient techniques to a crystall ographic R of 0.22 based on 16,482 unique reflections between 20.0 and 2.9 Angstrom. The free antiidiotypic Fab shows, when compared to its complexed form, a 5 degrees rotation of its variable light with respec t to its variable heavy domain and rearrangement of complementarity de termining region loops, which permits optimization of the stereocomple mentarity between interacting molecules. This finding supports the ind uced fit hypothesis for antibody antigen interaction.