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• HLA-DQA1 is one of the HLA class II alpha chain paralogues. HLA-DQB1 belongs to the HLA class II beta chain paralogs. This class II molecule is a heterodimer consisting of an alpha (DQA) and a beta (DQB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. 
• The exons 1-6 of mouse I-Ab1 gene that encodes the full-length protein of I-Ab1 was replaced by a chimeric CDS sequence encoding the α chain of HLA-DQ and a chimeric CDS sequence encoding the β chain of HLA-DQ in B-hHLA-DQ8 mice. The promoter sequence was derived from I-Ea gene. The following sequences were the chimeric CDS of humanized β chain including the β1 domain of human HLA-DQB1*03:02 and the β2, transmembrane, cytoplasmic domains of mouse I-Ab1 gene. The last sequences were the chimeric CDS of humanized α chain including the α1 domain of human HLA-DQA1*03:01 and the α2, transmembrane, cytoplasmic domains of mouse I-Aa gene. The mouse I-A protein was not detectable in the B-hHLA-DQ8 mice because the mouse I-A gene was disrupted.
• Human HLA-DQ was exclusively detectable in homozygous B-hHLA-DQ8 mice, but not in wild-type C57BL/6JNifdc mice.
• B-hHLA-DQ8 mice provide a powerful preclinical model for in vivo evaluation of vaccines and research on autoimmune diseases.
• Application: For example, this product is used for pharmacodynamics and safety evaluation of vaccines for cancers and research on autoimmune diseases.

Gene targeting strategy for B-hHLA-DQ8 mice. The exons 1-6 of mouse I-Ab1 gene that encodes the full-length protein of I-Ab1 was replaced by a chimeric CDS sequence encoding the α chain of HLA-DQ and a chimeric CDS sequence encoding the β chain of HLA-DQ in B-hHLA-DQ8 mice. The promoter sequence was derived from I-Ea gene. The following sequences were the chimeric CDS of humanized β chain including the β1 domain of human HLA-DQB1*03:02 and the β2, transmembrane, cytoplasmic domains of mouse I-Ab1 gene. The last sequences were the chimeric CDS of humanized α chain including the α1 domain of human HLA-DQA1*03:01 and the α2, transmembrane, cytoplasmic domains of mouse I-Aa gene. The mouse I-A protein was not detectable in the B-hHLA-DQ8 mice because the mouse I-A gene was disrupted.

Strain specific HLA-DQ expression analysis in wild-type C57BL/6JNifdc mice and homozygous B-hHLA-DQ8 mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous humanized B-hHLA-DQ8 mice (H/H), respectively, and analyzed by flow cytometry with species-specific anti-mouse I-A/I-E antibody (Biolegend, 107607), and species-specific anti-human HLA-DQ antibody (Biolegend, 318106). Human HLA-DQ was exclusively detectable in homozygous B-hHLA-DQ8 mice, but not in wild-type C57BL/6JNifdc mice.

Strain specific HLA-DQ expression analysis in wild-type C57BL/6JNifdc mice and homozygous B-hHLA-DQ8 mice by flow cytometry. Blood cells were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous humanized B-hHLA-DQ8 mice (H/H), respectively, and analyzed by flow cytometry with species-specific anti-mouse I-A/I-E antibody (Biolegend, 107607), and species-specific anti-human HLA-DQ antibody (Biolegend, 318106). Human HLA-DQ was exclusively detectable in homozygous B-hHLA-DQ8 mice, but not in wild-type C57BL/6JNifdc mice.

Strain specific HLA-DQ expression analysis in wild-type C57BL/6JNifdc mice and homozygous B-hHLA-DQ8 mice by flow cytometry. Bone marrow cells were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous humanized B-hHLA-DQ8 mice (H/H), respectively, and analyzed by flow cytometry with species-specific anti-mouse I-A/I-E antibody (Biolegend, 107607), and species-specific anti-human HLA-DQ antibody (Biolegend, 318106). Human HLA-DQ was exclusively detectable in homozygous B-hHLA-DQ8 mice, but not in wild-type C57BL/6JNifdc mice.