3-DIMENSIONAL STRUCTURE OF AN IDIOTOPE ANTI-IDIOTOPE COMPLEX

SEROLOGICALLY detected antigenic determinants unique to an antibody or group of antibodies1-3 are called idiotopes. The sum of idiotopes of an antibody constitute its idiotype3. Idiotypes have been intensively studied following a hypothesis for the self-regulation of the immune system through a network of idiotype-anti-idiotype interactions4. Furthermore, as antigen and anti-idiotypes can competitively bind to idiotype-positive, antigen-specific antibodies, anti-idiotypes may carry an 'internal image' of the external antigen (see refs 5-10 for reviews). Here we describe the structure of the complex between the monoclonal anti-lysozyme FabD1.3 and the anti-idiotopic FabE225 at 2.5 Å resolution. This complex defines a private idiotope consisting of 13 amino-acid residues, mainly from the complementarity-determining regions of D1.3. Seven of these residues make contacts with the antigen, indicating a significant overlap between idiotope and antigen-combining site. Idiotopic mimicry of the external antigen is not achieved at the molecular level in this example. © 1990 Nature Publishing Group.