Immune responses against Aβ1-42 in HLA class II transgenic mice: Implications for Aβ1-42 immune-mediated therapies

Pritam Das, Svetlana Chapoval, Victor Howard, Chella S. David, Todd E. Golde

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)969-976
Number of pages8
JournalNeurobiology of aging
Volume24
Issue number7
DOIs
StatePublished - Nov 2003

Keywords

  • Alzheimer's disease
  • Aβ vaccination
  • Aβ1-42
  • MHC class II
  • Tg2576 mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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