ANTIBODY REPERTOIRE IN THE RESPONSE TO A PROTEIN ANTIGEN - INTERRELATED IDIOTYPIC FAMILIES IN THE RESPONSE TO IA.7

Mouse alloantibodies to Ia.7 display a cross-reactive idiotype (CRI) r ecognized by xenogeneic anti-idiotypes. The CRI is expressed on serum Abs in all responding individuals and on all anti-Ia.7 mAbs, from mice of appropriate genetic types. In addition, both xenogeneic and alloge neic anti-idiotypes in this system have a striking ability to induce I a.7-specific responses in mice never exposed to the Ag. Because of the se unusual features, we have investigated the biologic and structural basis of the idiotypic sharing in this system. Ia.7-specific Ab popula tions induced by eight different Ab2 mAbs were analyzed for expression of each of the set of idiotopes. Two obvious explanations for the unu sual properties of the system do not appear to be correct. 1) The indu ction of Ag-specific immunity was not caused by internal imagery; and 2) the Ab2s do not simply recognize the same idiotope, because they in duce populations that were found to be distinct in idiotope expression . The biologic properties of the system are instead caused by a patter n of expression of idiotope sets on distinct but related Ab families, and a remarkable linkage of a series of different idiotopes to Ia.7-sp ecific activity. Mouse anti-idiotypic responses failed to recognize th e widely shared CRI site, even when sequential immunizations were perf ormed. To examine the structural basis of Id sharing, light chains of three CRI(+) mAbs were sequenced. They were found to be extremely homo logous to each other and to the germ-line V kappa 21E gene, and they u sed either J1 or J2. A model containing families of distinct but relat ed V regions is proposed for the anti-Ia.7 repertoire.