Whereas humanized mouse models have contributed significantly to human immunology research, human T cells developing in mouse thymic environment fail to demonstrate HLA-restricted function.To achieve HLA-restricted human immune response, we created NOD/SCID/IL2rg null strain (B-NDG) with homozygous expression of HLA class I heavy chain and lightchain (B-NDG HLA 2.1 mice). The model B2m gene (Exon1 to Exon3) of mouse were replaced by the sequence encompassing the human B2M CDS and HLA-A*0201 gene. The HLA-expressing humanized mouse with functional HLA-restricted T cells and consistent representation of rare T-cell subsets overcomes a major constraint in human immunology, and serves as a useful model for investigation of human immune responses against pathogens and for the development of therapeutic strategies against human diseases.
Protein expression analysis (heterozygous mice)
Strain specific B2M and HLA expression analysis in heterozygous B-NDG HLA-A2.1 mice by flow cytometry. Splenocytes from both wild type (+/+) C57BL/6 and heterozygous B-NDG HLA-A2.1 (H/+) mice were analyzed by flow cytometry. Mouse B2M and H-2K/H-2D were detectable in the WT C57BL/6 and heterozygous B-NDG HLA-A2.1 mice. Human B2M and HLA-A2 were only detectable in the heterozygous B-NDG HLA-A2.1 mice.