Immune responses against Abeta1-42 in HLA class II transgenic mice: implications for Abeta1-42 immune-mediated therapies.
We have investigated whether polymorphic differences in the major histocompatibility complex (MHC) class II molecules influence humoral and cellular immune responses against Abeta1-42. To analyze the effects of mouse MHC class II and tolerance effects of overexpression of human APP in mice, we immunized Tg2576 and non-transgenic littermates bred into two different MHC backgrounds with Abeta1-42 and compared both B and T cell responses. We found that in the presence of the mouse C57BL/6 background, both B and T cell responses against Abeta1-42 were significantly suppressed. To directly test the contribution of human MHC class II, we immunized various human HLA class II transgenic (TG) mice with Abeta1-42 and analyzed anti-Abeta immune responses. HLA-DR3 and HLA-DQ8 TG mice generated modest B and T cell responses against Abeta1-42. The presence of HLA-DR3/DQ8 in double TG mice enhanced the overall immune response against Abeta1-42. In contrast, HLA-DR4 TG mice mounted strong T cell responses but failed to generate high titer antibody responses against Abeta1-42, whereas, the HLA-DQ6 TG mice were not able to mount significant B or T cell responses against Abeta1-42. These studies in mice suggest that the presence of certain MHC class II molecules or combinations of class II molecules can potentially influence the overall immune response against Abeta1-42.
Das
Pritam
P
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Chapoval
Svetlana
S
Howard
Victor
V
David
Chella S
CS
Golde
Todd E
TE
D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D005802:Genes, MHC Class II / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007114:Immunization; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology* / Q000494:pharmacology; D011110:Polymorphism, Genetic; D013045:Species Specificity
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)