Immune responses against Aβ1–42 in HLA class II transgenic mice: implications for Aβ1–42 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 Aβ1–42. 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 Aβ1–42 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 Aβ1–42 were significantly suppressed. To directly test the contribution of human MHC class II, we immunized various human HLA class II transgenic (TG) mice with Aβ1–42 and analyzed anti-Aβ immune responses. HLA-DR3 and HLA-DQ8 TG mice generated modest B and T cell responses against Aβ1–42. The presence of HLA-DR3/DQ8 in double TG mice enhanced the overall immune response against Aβ1–42. In contrast, HLA-DR4 TG mice mounted strong T cell responses but failed to generate high titer antibody responses against Aβ1–42, whereas, the HLA-DQ6 TG mice were not able to mount significant B or T cell responses against Aβ1–42. 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 Aβ1–42.