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) recognized 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 allogeneic anti-idiotypes in this system have a striking ability to induce Ia.7-specific responses in mice never exposed to the Ag. Because of these unusual features, we have investigated the biologic and structural basis of the idiotypic sharing in this system. Ia.7-specific Ab populations induced by eight different Ab2 mAbs were analyzed for expression of each of the set of idiotopes. Two obvious explanations for the unusual properties of the system do not appear to be correct. 1) The induction of Ag-specific immunity was not caused by internal imagery; and 2) the Ab2s do not simply recognize the same idiotope, because they induce populations that were found to be distinct in idiotope expression. The biologic properties of the system are instead caused by a pattern of expression of idiotope sets on distinct but related Ab families, and a remarkable linkage of a series of different idiotopes to Ia.7-specific activity. Mouse anti-idiotypic responses failed to recognize the widely shared CRI site, even when sequential immunizations were performed. To examine the structural basis of Id sharing, light chains of three CRI+ mAbs were sequenced. They were found to be extremely homologous to each other and to the germ-line V kappa 21E gene, and they used either J1 or J2. A model containing families of distinct but related V regions is proposed for the anti-Ia.7 repertoire.
Misplon
J A
JA
Molecular Immunology Laboratory, CBER, Food and Drug Administration, Bethesda, MD 20892.
Wood
T
T
Harvath
L
L
Epstein
S L
SL
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D003429:Cross Reactions; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007130:Immunoglobulin Idiotypes