Epitopes described in "Characterization of murine immunoglobulin G antibodies against human amyloid-beta1-42."

Article Authors:T Town; J Tan; N Sansone; D Obregon; T Klein; M Mullan
Article Title:Characterization of murine immunoglobulin G antibodies against human amyloid-beta1-42.
Reference Detail
Reference ID:1014416
Abstract:It has been demonstrated that immunization of transgenic mouse models of Alzheimer's disease (AD) with amyloid-beta1-42 peptide (Abeta1-42) results in amelioration of AD-like pathology, including reduced soluble and deposited beta-amyloid and decreased cognitive impairment. Based on the proposed importance of immunoglobulin G (IgG) anti-Abeta antibodies (Abs) in these effects, we sought to characterize these Abs in splenocytes from mice immunized with Abeta1-42. Data show that a more aggregated preparation of Abeta1-42 gives a robust IgG anti-Abeta Ab response, while these Abs are almost undetectable when a less aggregated preparation of Abeta1-42 is used as the immunogen. Importantly, IgG anti-Abeta Ab production is detected after just 12 weeks of Abeta1-42 treatment. Analysis of anti-Abeta Ab IgG isotypes reveals that the majority of these Abs are IgG1, with significantly fewer Abs of the IgG2a or IgG2b isotypes (IgG1>IgG2a>IgG2b), suggesting a T lymphocyte helper type II response after Abeta1-42 immunization. To determine the epitope of Abeta recognized by IgG anti-Abeta Abs, intact Abeta and Abeta peptide fragments were analyzed for their ability to bind these Abs. Data show that these Abs specifically recognize an amino-terminal epitope of Abeta between amino acids one and twelve, with higher affinity for a more soluble preparation of Abeta1-42. These data further indicate the immunogenic potential of Abeta1-42 and offer insight into the nature of the IgG anti-Abeta Ab response.
Affiliations:The Roskamp Institute, University of South Florida, 3515 E. Fletcher Avenue, Tampa, FL 33613, USA. ttown@hsc.usf.edu
Reference Type:Literature
PubMed ID:11427310
Journal:Neurosci Lett
Journal Volume:307
Article Pages:101-4
Journal ISSN:0304-3940
Article Chemical List:Amyloid beta-Peptides;Epitopes;Immunoglobulin G;Isoantibodies;Peptide Fragments;amyloid beta-protein (1-42)
Article MeSH List:Alzheimer Disease(immunology; physiopathology; therapy); Amyloid beta-Peptides(immunology); Animals; Antibody Specificity(immunology); Cells, Cultured(cytology; immunology; metabolism); Epitopes(immunology; metabolism); Immunoglobulin G(immunology; isolation & purification; metabolism); Immunotherapy; Isoantibodies(immunology; metabolism); Mice; Mice, Inbred C57BL; Peptide Fragments(immunology; metabolism); Spleen(cytology; immunology; metabolism)
Curation Last Updated:2014-10-03 21:29:58