Mouse alloantibodies to Ia.7 display a cross-reactive idiotype (CRI) that is recognized by xenogeneic anti-idiotype, is expressed in all responders of appropriate strains, and is found on all monoclonal anti- Ia.7 antibodies. In addition, both xenogeneic and allogeneic anti- idiotypes in this system have striking ability to induce Ia.7-specific responses in mice never exposed to the antigen, providing a model for idiotypic vaccination. We have investigated the biological and structural features of the repertoire that form the basis of idiotypic sharing in this system. Internal imagery was ruled out as an explanation for the idiotype induction. Ia.7-specific antibody populations induced by eight different Ab2 monoclonal antibodies were analyzed for expression of each of the set of idotopes, and the populations found to be distinct in patterns of idiotope expression. Mouse anti-idiotypic responses failed to recognize the widely shared CRI site, even when sequential immunizations were performed. To examine the structural basis of idiotype sharing, light chains of representative idiotype-positive mAbs were sequenced under a contract with the laboratories of Drs. Tom Wood and Matthew Gonda, PRI, FCRF, and found to be extremely homologous with each other and with the germ line V-kappa- k21E gene. J1 and J2 were both expressed on CRI+ mAbs. We have proposed a model of overlapping idiotypic families to explain the repertoire and biological properties of this response.
