Anti-angiotensin II anti-idiotypic antibodies bind to angiotensin II receptor.

An anti-idiotypic serum from a rabbit immunized with one anti-angiotensin II (AII) monoclonal antibody (A25) was shown to identify a cross-reactive idiotope (CRI) shared by six anti-AII monoclonal antibodies, in addition to a binding site-associated private idiotope. This anti-idiotypic reagent bound to rat liver membranes bearing AII receptors; binding was abolished after pretreatment of the membranes with AII. In immunoblotting experiments with rat liver membranes, as well as with rat pituitary homogenates, a 63,000 +/- 2,000 dalton protein was revealed that co-migrated with the AII receptor. After purification by affinity chromatography on an immobilized CRI+-antibody (A41), anti-CRI antibodies could immunoprecipitate the hormone binding activity from detergent-treated rat liver membranes and still recognize the 63,000 dalton protein. In contrast, anti-idiotypic antibodies specific for the private idiotope failed to interact with the AII receptor. Similar results were obtained with a second anti-idiotypic serum produced by immunization with another CRI+ anti-AII monoclonal antibody (A22). The sharing of the CRI determinant between the AII receptor and anti-AII antibodies might account for the reactivity of anti-idiotypic antibodies towards the AII receptor.