Description
- HLA-DRA is one of the HLA class II alpha chain paralogues. HLA-DRB1 belongs to the HLA class II beta chain paralogs. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) 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. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5.
- The exon 2 of mouse I-Ea gene that encodes the extracellular domain of I-Ea was replaced by human HLA-DRA encoding the α1 domain in B-hHLA-DRB1*4.1 mice. The exon 2 of mouse I-Eb1 gene that encodes the extracellular domain of I-Eb1 was replaced by human HLA-DRB encoding the β1 domain in B-hHLA-DRB1*4.1 mice. The mouse I-Aa, I-Ab1 and I-Eb2 were knocked out in B-hHLA-DRB1*4.1 mice.
- Human HLA-DR was exclusively detectable in homozygous B-hHLA-DRB1*4.1 mice, but not in wild-type C57BL/6 mice.
- B-hHLA-DRB1*4.1 mice provide a powerful preclinical model for in vivo evaluation of vaccines.
- Application: For example, this product is used for pharmacodynamics and safety evaluation of vaccines for cancers.
Targeting strategy
Gene targeting strategy for B-hHLA-DRB1*4.1 mice.
The exon 2 of mouse I-Ea gene that encodes the extracellular domain of I-Ea was replaced by human HLA-DRA encoding the α1 domain in B-hHLA-DRB1*4.1 mice. The exon 2 of mouse I-Eb1 gene that encodes the extracellular domain of I-Eb1 was replaced by human HLA-DRB encoding the β1 domain in B-hHLA-DRB1*4.1 mice. The mouse I-Aa, I-Ab1 and I-Eb2 were knocked out in B-hHLA-DRB1*4.1 mice.
Protein expression analysis in blood
Strain specific HLA-DRB1 expression analysis in wild-type C57BL/6 mice and homozygous B-hHLA-DRB1*4.1 mice by flow cytometry. Blood cells were collected from wild-type C57BL/6 mice (+/+) and homozygous humanized B-hHLA-DRB1*4.1 mice, respectively, and analyzed by flow cytometry with species-specific anti-mouse I-A/I-E antibody (Biolegend, 107607), and species-specific anti-human HLA-DR antibody (Biolegend, 362303). Human HLA-DRB1 was exclusively detectable in homozygous B-hHLA-DRB1*4.1 mice , but not in wild-type C57BL/6 mice.
* When publishing results obtained using this animal model, please acknowledge the source as follows: The animal model [B-hHLA-DRB1*4.1 mice] (Cat# 112900) was purchased from Biocytogen.
