Anti-immunoglobulin antibodies. III. Properties of sequential anti- idiotypic antibodies to heterologous anti-gamma globulins. Detection of reactivity of anti-idiotype antibodies with epitopes of Fc fragments (homobodies) and with epitopes and idiotopes (epibodies)

Murine anti-V region antibodies against a human monoclonal protein Gl with anti-gamma-globulin activity and bearing the Wa cross-reactive idiotype were prepared in several strains of mice. Antibodies were obtained that were specific for the Gl idiotype, the Wa cross-reactive idiotype, and for various framework antigenic determinants that were distinguished by a variety of procedures. Synthesis of such antibodies were found to be independent of MHC and Igh gene complexes. These anti-V region antibodies, produced by a majority of mouse strains investigated, also share a cross-reactive idiotype recognized by BALB/c anti-anti-V region Gl antibodies. A fraction of BALB/c anti-anti-V region Gl antibodies displayed human Fc gamma binding activity and, therefore, can be considered homobodies, as described in other systems. Two of the anti-idiotype antibodies obtained in this system exhibited a peculiar property: they interacted not only with their own antigen (IgM Gl), but also with the Fc fragment with which IgM Gl reacts. Thus, A/J anti-V region Gl antibodies bind to the human Fc gamma fragment in addition to IgM Gl. Similarly, a monoclonal CB6 F1 anti-anti-V region Gl antibody interacted with the V region of IgM Gl as well as with the syngeneic anti-V region antibodies. We called these anti-idiotypic antibodies epibodies because they interact with epitopes of the primary antigen. These homobodies and epibodies, obtained by immunization across heterologous barriers, represent new examples of recognition of the internal image of the antigen within the immune system.