Crystal structure of an Fv-Fv idiotope-anti-idiotope complex at 1.9 A resolution.

Abstract Anti- idiotopicantibodies react with unique antigenic features, usually associated with the combining sites, of other antibodies. They may thus mimic specific antigens that react with the same antibodies. The structural basis of this mimicryis analyzed here in detail for an anti- idiotopicantibody that mimics the antigen, hen egg-white lysozyme. The crystal structure of an anti-hen- egg-white lysozymeantibody (D1.3) complexed with an anti- idiotopicantibody (E5.2) has been determined at a nominal resolution of 1.9 A. E5.2 contacts substantially the same residues of D1.3 as lysozyme, thus mimicking its binding to D1.3. The mimicryembodies conservation of hydrogen bonding: six of the 14 protein – protein hydrogen bonds bridging D1.3-E5.2 are structurally equivalent to hydrogen bonds bridging D1.3- lysozyme. The mimicryincludes a similar number of van der Waals interactions. The mimicryof E5.2 for lysozyme, however, does not extend to the topology of the non-polar surfaces of E5.2 and lysozyme, which are in contact with D1.3 as revealed by a quantitative analysis of the contacting surface similarities between E5.2 and lysozyme. The structure discussed herein shows that an anti- idiotopicantibody can provide an approximate topological and binding-group mimicryof an external antigen, especially in the case of the hydrophilic surfaces, even though there is no sequence homology between the anti- idiotopeand the antigen.