Anti-idiotypic antibodies against the kinin receptor.
Three sets of monoclonal antibodies against bradykinin (MBK1, MBK2, MBK3) were generated by somatic cell fusion, characterized by their peptide specificity and compared to the known ligand specificity of the kinin receptor subtypes. By these criteria the paratope of MBK3 resembled the B2 receptor binding site whereas MBK1 shared principal binding characteristics with the B1 recrptor. Anti-idiotypic antibodies against MBK1, MBK2 and MBK3 were raised in rabbit and sheep. Specificity of the network components was verified by inhibition experiments on the level of peptide, idiotype and anti-idiotype. Anti-idiotypic antibodies against MBK3 recognized a conformation-dependent epitope which was binding site-related. Binding studies on human foreskin fibroblasts and guinea pig ileum showed mutual displacement of the anti-idiotypic antibody and bradykinin at the binding site pointing to a specific interaction of the antibody with the receptor from various species. An agonist activity of the antibodies, demonstrated in human (inositolphosphate pathway) and mouse (prostaglandin pathway) fibroblasts indicated that the anti-idiotypes bear an internal image of the ligand epitope. This molecular mimicry which was further substantiated by the detection of bradykinin specific anti-idiotypic antibodies, provides the structural basis for the observed cross-reactivity over species borders.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D001667:Binding, Competitive; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D016234:Kallikrein-Kinin System / Q000276:immunology; D007705:Kinins / Q000378:metabolism*; D051379:Mice; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000145:classification / Q000276:immunology* / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007705:Kinins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D001920:Bradykinin