Species-specific immune response to immunization with human versus rodent A beta peptide.
Amyloid beta (A beta) immunization of amyloid precursor protein (APP)-transgenic (tg) mice with human A beta induces humoral immunity, however, the immune response to endogenous rodent A beta is unknown. Fourteen-month J20 APP-tg mice and non-tg littermates were immunized subcutaneously followed by chronic intranasal boosting with human or rodent A beta peptide and adjuvant LT(R192G). Rodent A beta-immunized APP-tg mice had anti-rodent A beta antibody levels of 257.8 micrograms/ml and those immunized with human A beta had anti-human A beta antibodies of 120.8 micrograms/ml. Non-tg littermates had anti-rodent and anti-human A beta antibody concentrations of 98.8 and 231.1 microgram/ml, respectively. Inter-species cross-reactivity was minimal. Anti-human A beta antibodies were predominately IgG1 and IgG2b, while anti-rodent A beta antibodies were equally IgG1, IgG2a, and IgG2b. Anti-human A beta antibodies recognized an epitope within human A beta1-9. Anti-rodent A beta antibodies did not stain Alzheimer's disease (AD) plaques but bound some plaques in APP-tg mice. Splenocytes proliferated modestly to their respective antigen and secreted low levels of IL-2 and IFN-gamma. Therefore, immunizing APP-tg and non-tg mice with rodent A beta resulted in a species-specific humoral response with modest T cell reactivity.
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Timothy J
TJ
Seabrook
Jeanne K
JK
Bloom
Melitza
M
Iglesias
Edward T
ET
Spooner
Dominic M
DM
Walsh
Cynthia A
CA
Lemere
D000544:Alzheimer Disease / Q000276:immunology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D030801:Animals, Genetically Modified; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D051379:Mice; D058225:Plaque, Amyloid / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
D016229:Amyloid beta-Peptides; D000906:Antibodies; D000939:Epitopes; D007074:Immunoglobulin G; D007376:Interleukin-2; D007371:Interferon-gamma