STRUCTURE OF IDIOTYPE-ANTI-IDIOTYPE INTERACTIONS

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The chemical bases of antigenic determinants and of their recognition by specific antibody molecules in immune responses have been explored in numerous studies using immunological and physiochemical techniques. In spite of this intense research activity, several questions remain unanswered, such as those concerning the conformation of antigenic determinants (continuous or topographical), the effect of structural changes (such as amino acid replacements) on their recognition by specific antibodies, and the nature of conformational changes in the antigen after immune complex formation. Equally interesting are questions concerning the structural bases of antibody action, such as the physical extent of the antigen recognition sites, the nature of conformational changes taking place in the antibody molecule after the formation of immune complexes and the nature of the chemical bonds that give rise to the specificity and stability of those complexes. A special case of antigen-antibody interactions is that in which the antigenic determinant is the idiotope of an antibody and in which the anti-idiotope antibody mimics the antigen, thus providing an "internal image" of that antigen. Idiotype/anti-idiotype interactions constitute the bases for postulated regulatory mechanisms of the immune system. The mimicking of foreign antigens by anti-idiotope antibodies has been as the basis for immunization against diverse antigens, a possible practical application. In order to study the problems outlined above this laboratory has used the technique of cellular hybridization to obtain monoclonal antibodies directed against hen egg-white lysozyme. This protein as chosen as the antigen because of its well characterized three- dimensional structure, immunogenicity and availability. In addition, a specific anti-lysozyme antibody, D1:3, which recognizes a well defined antigenic determinant has been used to obtain anti-idiotopic antibodies, and complexes between these antibodies and D1.3 have been submitted to crystallization trials. A crystalline complex has thus been obtained and will be submitted to X-ray diffraction studies. These studies should provide the structural definition of a combining-site related idiotope and should enable to compare the three-dimensional structure of the anti-idiotopic antibody with that of the external antigen.