CRYSTAL-STRUCTURE OF AN FV-FV IDIOTOPE - ANTI-IDIOTOPE COMPLEX AT 1.9ANGSTROM RESOLUTION

Anti-idiotopic antibodies react with unique antigenic features, usuall y associated with the combining sites, of other antibodies. They may t hus mimic specific antigens that react with the same antibodies. The s tructural basis of this mimicry is analyzed here in detail for an anti -idiotopic antibody that mimics the antigen, hen egg-white lysozyme. T he crystal structure of an anti-hen-egg-white lysozyme antibody (D1.3) complexed with an anti-idiotopic antibody (E5.2) has been determined at a nominal resolution of 1.9 Angstrom. E5.2 contacts substantially t he same residues of D1.3 as lysozyme, thus mimicking its binding to D1 .3. The mimicry embodies 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 mimicry inclu des a similar number of van der Waals interactions. The mimicry of E5. 2 for lysozyme, however, does not extend to the topology of the non-po lar surfaces of E5.2 and lysozyme, which are in contact with D1.3 as r evealed by a quantitative analysis of the contacting surface similarit ies between E5.2 and lysozyme. The structure discussed herein shows th at an anti-idiotopic antibody can provide an approximate topological a nd binding-group mimicry of an external antigen, especially in the cas e of the hydrophilic surfaces, even though there is no sequence homolo gy between the anti-idiotope and the antigen. (C) 1996 Academic Press Limited