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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Amyloid, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Antibodies, Anti-Idiotypic, Antibody Specificity, Complementarity Determining Regions, Epitope Mapping, Immunoglobulin G, Immunoglobulin Heavy Chains, Immunoglobulin M, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Models, Animal, Protein Conformation.
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Do heavy-chain complementarity-determining regions determine conformation selectivity of anti-aβ antibodies? Context: Amyloid-β (Aβ) protofibrils are neurotoxic soluble intermediates in the Aβ aggregation process eventually forming senile plaques in Alzheimer's disease. This Aβ species is a potential biomarker for Alzheimer's disease and also a promising target for immunotherapy. In this study, we investigated the characteristics of conformation-dependent Aβ antibodies specific for Aβ protofibrils. Mice were immunized with Aβ protofibrils to generate hybridomas producing Aβ-specific monoclonal antibodies. Binding of antibodies to different Aβ conformations was investigated with inhibition ELISA. The antibodies' complementarity-determining region (CDR) sequences were determined and compared. A majority of the antibodies were of the IgM class, all selectively binding to aggregated Aβ. Two IgG antibodies were generated: one with selective affinity for Aβ protofibrils and the other bound Aβ in all conformations. A high degree of similarity between the heavy-chain CDRs of the conformation-dependent antibodies was found, and all high-affinity Aβ antibodies displayed a high degree of sequence similarity in the light-chain CDRs.
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Sequence similarity in the heavy-chain CDRs is associated with conformation selectivity of the antibodies, while sequence similarity in the light-chain CDRs correlates with the affinity for Aβ. Final Decision: yes