Characterization of murine immunoglobulin G antibodies against human amyloid-beta1-42.
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.
Town
T
T
The Roskamp Institute, University of South Florida, 3515 E. Fletcher Avenue, Tampa, FL 33613, USA. ttown@hsc.usf.edu
Tan
J
J
Sansone
N
N
Obregon
D
D
Klein
T
T
Mullan
M
M
D000544:Alzheimer Disease / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology*; D002478:Cells, Cultured / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D007167:Immunotherapy; D007518:Isoantibodies / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000939:Epitopes; D007074:Immunoglobulin G; D007518:Isoantibodies; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)