Heavy-Chain Complementarity-Determining Regions Determine Conformation Selectivity of Anti-A beta Antibodies
2011 (English)In: Neurodegenerative Diseases, ISSN 1660-2854, Vol. 8, no 3, 117-123 p.Article in journal (Refereed) Published
Background/Aims: Amyloid-beta (Abeta) protofibrils are neurotoxic soluble intermediates in the Abeta aggregation process eventually forming senile plaques in Alzheimer's disease. This Abeta 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 Abeta antibodies specific for Abeta protofibrils. Methods: Mice were immunized with Abeta protofibrils to generate hybridomas producing Abeta-specific monoclonal antibodies. Binding of antibodies to different Abeta conformations was investigated with inhibition ELISA. The antibodies' complementarity-determining region (CDR) sequences were determined and compared. Results: A majority of the antibodies were of the IgM class, all selectively binding to aggregated Abeta. Two IgG antibodies were generated: one with selective affinity for Abeta protofibrils and the other bound Abeta in all conformations. A high degree of similarity between the heavy-chain CDRs of the conformation-dependent antibodies was found, and all high-affinity Abeta antibodies displayed a high degree of sequence similarity in the light-chain CDRs. Conclusion: 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 Abeta.
Place, publisher, year, edition, pages
2011. Vol. 8, no 3, 117-123 p.
Alzheimer's disease, Amyloid-beta, Conformation dependent antibodies, Complementarity determining region
Medical and Health Sciences
Research subject Geriatrics
IdentifiersURN: urn:nbn:se:uu:diva-132722DOI: 10.1159/000316530ISI: 000289100800003PubMedID: 20714111OAI: oai:DiVA.org:uu-132722DiVA: diva2:359006