Mapping of immune responses following wild-type and mutant ABeta42 plasmid or peptide vaccination in different mouse haplotypes and HLA Class II transgenic mice

HLA-DR Alleles in Amyloid β-Peptide Autoimmunity: A Highly Immunogenic Role for the DRB1*1501 Allele

“…Humanized HLA-DR4 Tg mice demonstrated significantly more T cell proliferation than humanized HLA-DR3 Tg or humanized HLA-DQ8 Tg mice after they were immunized with A␤, whereas no A␤-specific T cell proliferation response was exhibited by humanized HLA-DQ6 Tg mice (22). In mice bearing the HLA-DR allele DRB1*0101, A␤-specific T cell responses were mapped primarily to A␤1-28, similarly to those observed in C57BL/6 and BALBC mice (18).…”

“…First, the dominant T cell epitope in DR15 mice was found between residues 25 and 42, whereas it was found in A␤ peptides 10 -24, 16 -30, and 1-33 in SJL, C57BL6, and BALBC mice, respectively (17)(18)(19). Second, the amounts of IFN-␥ secreted as a consequence of in vitro stimulation of DR15-derived T cells were ϳ5-20 times higher than those observed with T cells derived from the highly immunogenic SJL strain (data not shown).…”

“…The extent of A␤ T cell activation differs significantly among mouse strains bearing different MHC class II (MHC-II) haplotypes (17)(18)(19)(20). For example, SJL mice, which bear the H-2 s haplotype, were substantially more A␤-immunogenic than C57BL/6 mice, which bear the H-2 b haplotype (19).…”

“…Clearance of A␤, achieved by A␤ vaccination, has been shown to prevent its deposition in the brain as well as the associated glial activation and cognitive deficits (7-14). In a clinical trial of AD patients, however, such treatment resulted in unexpected complications in the form of meningoencephalitis in ϳ6% of participants (15, 16), presumably caused by pathogenic activation of A␤-specific T cells in certain A␤-immunogenic individuals.The extent of A␤ T cell activation differs significantly among mouse strains bearing different MHC class II (MHC-II) haplotypes (17)(18)(19)(20). For example, SJL mice, which bear the H-2 s haplotype, were substantially more A␤-immunogenic than C57BL/6 mice, which bear the H-2 b haplotype (19).…”

Mammalian amyloidogenic proteins promote prion nucleation in yeast

“…The chimeric gene coding for Sup35N-PrP23-230 was constructed by inserting the PCR amplified BamHIXbaI fragment that codes for the region 23-230 of PrP from plasmid mPrPcyto [83] into the pmCUP1-Sup35NM-PrP90-230 vector at the position following the Sup35NM coding sequence, replacing the PrP90-230 coding fragment. The gene coding for Sup35NM-Aβ1-42 was constructed by inserting the PCR amplified EcoRI-NotI fragment that contains Aβ1-42 from the plasmid pcDNA3.1(+)-Aβ42 (kindly provided by Dr. K. Ugen, University of South Florida) containing the human Aβ1-42 coding sequence [84], into the pmCUP1-Sup35NM-PrP90-230 vector at the position following the Sup35NM coding sequence, replacing the PrP90-230 coding fragment. The DNA sequence coding for Aβ1-42 was placed under the P CUP1 promoter by inserting the PCR amplified BamHI-XbaI fragment that codes for Aβ1-42, from the plasmid pmCUP1-Sup35NM-Aβ1-42, into the pmCUP1 vector at the position following the P CUP1 promoter.…”