B-HLA-DRB1*15.1 mice

C57BL/6-H2-Eatm1(HLA-DRA1*1.1)Bcgen H2-Eb1tm1(HLA-DRB1*15.1)Bcgen H2-Atm1Bcgen H2-Eb2tm1Bcgen/Bcgen • 114524

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B-HLA-DRB1*1.1 mice(C)
B-HLA-DRB1*3.1 mice

B-HLA-DRB1*15.1 mice

Product nameB-HLA-DRB1*15.1 mice
Catalog number114524
Strain nameC57BL/6-H2-Eatm1(HLA-DRA1*1.1)Bcgen H2-Eb1tm1(HLA-DRB1*15.1)Bcgen H2-Atm1Bcgen H2-Eb2tm1Bcgen/Bcgen
Strain backgroundC57BL/6
NCBI gene ID100504404,14969,381091,14960,14961 (Mouse)
AliasesIa3; Ia-3; H-2Ea; H2-Ea-ps; I-Ealpha; E-alpha-f; MHC-H2-Ea; Eb; Ia4; H2Eb; Ia-4; H-2Eb; Ia5; Ia-5; H-2Eb2; Iebeta2; A130038H09Rik; Ia1; H2Aa; Ia-1; H-2Aa; Aalpha; IAalpha; I-Aalpha; IAb; Ia2; Ia-2; Abeta; H-2Ab; H2-Ab; Rmcs1; I-Abeta
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  • Description
  • Targeting strategy
  • Phenotypic analysis

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      Description

      HLA-DRB1*15.1: The mechanism of effector functions

      • Gene Information: The HLA-DRA1*01:01 and HLA-DRB1*15:01 genes encode the monomorphic alpha and highly polymorphic beta chains, respectively, which pair together to form the HLA-DR15 heterodimer, the strongest genetic risk factor for Multiple Sclerosis.
      • Protein Expression: This functional heterodimer is constitutively expressed on the surface of professional antigen-presenting cells (such as dendritic cells, macrophages, and B cells) to present exogenous peptides to the immune system.
      • Signaling Pathway: Upon loading a specific tumor or autoimmune peptide, the HLA-DR15 complex binds to the T-cell receptor (TCR), triggering downstream intracellular kinase cascades that drive CD4+ T-cell activation, proliferation, and cytokine secretion.
      • Therapeutic Inhibition: this complex serves as the target for designing high-affinity peptide vaccines (neoantigens or TAAs) that optimize HLA-DR15-binding to trigger potent, long-lasting anti-tumor CD4+ T-cell immunity.
      Targeting strategy

      HLA-DRB1*15.1

      • 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-HLA-DRB1*15.1 mice. The exon 2 of mouse I-Eb1 gene that encodes the extracellular domain of I-Eb1 was replaced by human HLA-DRB1*15.1 encoding the β1 domain in B-HLA-DRB1*15.1 mice. The  mouse I-Aa, I-Ab1 and I-Eb2 were knocked out in B-hHLA-DRB1*15.1 mice.
      HLA-DR Protein Expression Analysis
      • Mouse I-A/I-E was detected in wild-type (WT) C57BL/6JNifdc mice, but not in B-HLA-DRB1*15.1 mice.
      • Human HLA-DRB1*15.1 was exclusively detected in homozygous (HO) B-HLA-DRB1*15.1 mice.

      Mouse and human HLA-DRB1*15.1 expression analysis in splenocytes. Splenocytes were collected from wild-type C57BL/6JNifdc mice, homozygous B-HLA-DRB1*15.1 mice. HLA-DRB1*15.1 expression on various types of immune cells was analyzed by flow cytometry using species-specific anti-mouse I-A/I-E antibody (Biolegend, 107606) and anti-human HLA-DRB1 antibody (BioLegend, 307610).

      • Mouse I-A/I-E was detected in wild-type (WT) C57BL/6JNifdc mice, but not in B-HLA-DRB1*15.1 mice.
      • Human HLA-DRB1*15.1 was exclusively detected in homozygous (HO) B-HLA-DRB1*15.1 mice.

      Mouse and human HLA-DRB1*15.1 expression analysis in splenocytes. Splenocytes were collected from wild-type C57BL/6JNifdc mice, homozygous B-HLA-DRB1*15.1 mice. HLA-DRB1*15.1 expression on various types of immune cells was analyzed by flow cytometry using species-specific anti-mouse I-A/I-E antibody (Biolegend, 107606) and anti-human HLA-DRB1 antibody (BioLegend, 307610).

      • Mouse I-A/I-E was detected in wild-type (WT) C57BL/6JNifdc mice, but not in B-HLA-DRB1*15.1 mice.
      • Human HLA-DRB1*15.1 was exclusively detected in homozygous (HO) B-HLA-DRB1*15.1 mice.

      Mouse and human HLA-DRB1*15.1 expression analysis in blood. Blood cells were collected from wild-type C57BL/6JNifdc mice, homozygous B-HLA-DRB1*15.1 mice. HLA-DRB1*15.1 expression on various types of immune cells was analyzed by flow cytometry using species-specific anti-mouse I-A/I-E antibody (Biolegend, 107606) and anti-human HLA-DRB1 antibody (BioLegend, 307610).

      • Mouse I-A/I-E was detected in wild-type (WT) C57BL/6JNifdc mice, but not in B-HLA-DRB1*15.1 mice.
      • Human HLA-DRB1*15.1 was exclusively detected in homozygous (HO) B-HLA-DRB1*15.1 mice.

      Mouse and human HLA-DRB1*15.1 expression analysis in blood. Blood cells were collected from wild-type C57BL/6JNifdc mice, homozygous B-HLA-DRB1*15.1 mice. HLA-DRB1*15.1 expression on various types of immune cells was analyzed by flow cytometry using species-specific anti-mouse I-A/I-E antibody (Biolegend, 107606) and anti-human HLA-DRB1 antibody (BioLegend, 307610).

      • Mouse I-A/I-E was detected in wild-type (WT) C57BL/6JNifdc mice, but not in B-HLA-DRB1*15.1 mice.
      • Human HLA-DRB1*15.1 was exclusively detected in homozygous (HO) B-HLA-DRB1*15.1 mice.

      Mouse and human HLA-DRB1*15.1 expression analysis in bone marrow. Bone marrow cells were collected from wild-type C57BL/6JNifdc mice, homozygous B-HLA-DRB1*15.1 mice. HLA-DRB1*15.1 expression on various types of immune cells was analyzed by flow cytometry using species-specific anti-mouse I-A/I-E antibody (Biolegend, 107606) and anti-human HLA-DRB1 antibody (BioLegend, 307610).

      • Mouse I-A/I-E was detected in wild-type (WT) C57BL/6JNifdc mice, but not in B-HLA-DRB1*15.1 mice.
      • Human HLA-DRB1*15.1 was exclusively detected in homozygous (HO) B-HLA-DRB1*15.1 mice.

      Mouse and human HLA-DRB1*15.1 expression analysis in bone marrow. Bone marrow cells were collected from wild-type C57BL/6JNifdc mice, homozygous B-HLA-DRB1*15.1 mice. HLA-DRB1*15.1 expression on various types of immune cells was analyzed by flow cytometry using species-specific anti-mouse I-A/I-E antibody (Biolegend, 107606) and anti-human HLA-DRB1 antibody (BioLegend, 307610).

      Analysis of Leukocyte Subpopulations
      • The frequencies of T cells, B cells, NK cells, DCs, neutrophils, monocytes, and macrophages in homozygous B-HLA-DRB1*15.1 mice were similar to those in C57BL/6JNifdc mice.
      • Humanization of HLA-DRB1*15.1 does not affect normal immune cell development or distribution.

      Analysis of leukocyte subpopulations by flow cytometry in immune organs and blood. Splenocytes, peripheral blood, lymph nodes, and bone marrows were isolated from C57BL/6JNifdc and B-HLA-DRB1*15.1 mice (female, 15-week-old, n = 3). Single live cells were gated on the CD45⁺ population and analyzed by flow cytometry as indicated. Values are expressed as mean ± SEM.

      Analysis of T Cell Subpopulations
      • The proportions of CD4⁺ T cells, CD8⁺ T cells, and Tregs in homozygous B-HLA-DRB1*15.1 mice were comparable to those in C57BL/6JNifdc mice other than the lymph nodes where the frequency of CD8+ T cells were significantly decreased while the pfrequendy of CD4+ T cells were significantly increased .
      • Humanization of HLA-DRB1*15.1 does not affect normal T cell development, differentiation, or distribution.

      Analysis of T-cell subpopulations by flow cytometry in immune organs and blood. Splenocytes, peripheral blood, lymph nodes, and bone marrows were isolated from C57BL/6JNifdc and B-HLA-DRB1*15.1 mice (female, 15-week-old, n = 3). Single live cells were gated on the CD3⁺ T-cell population and analyzed by flow cytometry as indicated. Values are expressed as mean ± SEM.

      * When publishing results obtained using this animal model, please acknowledge the source as follows: The animal model [B-HLA-DRB1*15.1 mice] (Cat# 114524) was purchased from Biocytogen.