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B-hCD94/hNKG2A mice​
Strain Name C57BL/6-Klrd1tm1(KLRD1)Klrc1tm1(KLRC1)/Bcgen Common Name  B-hCD94/hNKG2A mice
Background C57BL/6 Catalog number  121077
Related Genes 
CD94,KLRD1, NKG2A, KLRC1, CD159a
Gene description


Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. KLRD1 (CD94) is an antigen preferentially expressed on NK cells and is classified as a type II membrane protein because it has an external C terminus. KLRC1 (NKG2A) is also a type II transmembrane protein which dimerize with CD94 molecule. CD94 contains a short cytoplasmic domain and it is responsible for signal transduction. CD94/NKG2 is a family of C-type lectin receptors which are expressed predominantly on the surface of NK cells and a subset of CD8+ T-lymphocyte. These receptors stimulate or inhibit cytotoxic activity of NK cells, therefore they are divided into activating and inhibitory receptors according to their function. CD94/NKG2 recognize non-classical MHC glycoproteins class I (HLA-E in human and Qa-1 molecules in the mouse). NKG2A receptor transmit inhibitory signal and contains two Immuno-receptor tyrosine-based inhibitory motives (ITIM) in the cytoplasmic tail that are defined by the sequence (I/L/V/S)xYxx(L/V), where “x” means any amino acid at a given position. If ITIM-bearing receptors engage their ligand, probably Src family kinase phosphorylates tyrosine residue, and this allows recruitment of the tyrosine phosphatase SHP-1, SHP-2 or SHIP. It leads to de-phosphorylation of tyrosine kinase’s substrates, which are involved in the activating cascades. As a result, NK cell activation is suppressed. 


mRNA expression analysis


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Strain specific analysis of CD94 and NKG2A gene expression in WT and homozygous B-hCD94/hNKG2A mice by RT-PCR. Mouse Cd94 and Nkg2a mRNA were detectable in splenocytes of wild-type (+/+) mice. Human CD94 and NKG2A mRNA were detectable only in the homozygous B-hCD94/hNKG2A, but not in +/+ mice. 


 Protein expression analysis in NK cells


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Strain specific CD94 and NKG2A expression analysis in homozygous B-hCD94/hNKG2A mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hCD94/hNKG2A (H/H) mice, and analyzed by flow cytometry with species-specific CD94 or NKG2A antibody. Mouse CD94 and NKG2A were detectable in WT mice. Human CD94 and NKG2A were exclusively detectable in homozygous B-hCD94/hNKG2A but not WT mice. (Monalizumab was  used to detect the human NKG2A protein in WT and homozygous B-hCD94/hNKG2A)


Protein expression analysis in activated CD8+ T cells


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Strain specific NKG2A expression analysis in homozygous B-hCD94/hNKG2A mice by flow cytometry. Splenocytes were collected from homozygous B-hCD94/hNKG2A (H/H) mice, and analyzed by flow cytometry with species-specific NKG2A antibody. Human NKG2A were exclusively detectable in activated CD8+ T cells of homozygous B-hCD94/hNKG2A mice after treated with mCD3e 24h. 


Protein expression analysis in activated CD8+ T cells

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Strain specific CD94 expression analysis in homozygous B-hCD94/hNKG2A mice by flow cytometry. Splenocytes were collected from homozygous B-hCD94/hNKG2A (H/H) mice, and analyzed by flow cytometry with species-specific CD94 antibody. Human CD94 were exclusively detectable in activated CD8+ T cells of homozygous B-hCD94/hNKG2A mice after treated with mCD3e 24h.


Analysis of spleen leukocyte subpopulations in B-hCD94/hNKG2A mice

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Analysis of splenic leukocyte subpopulations by FACS
Splenocytes were isolated from female C57BL/6 and B-hCD94/hNKG2A mice (n=3, 6 weeks-old) and analyzed by flow cytometry to assess leukocyte subpopulations. (A) Representative FACS plots gated on single live CD45+ cells for further analysis. (B) Results of FACS analysis. Percentages of T, B, NK cells, monocytes/macrophages, and DC were similar in homozygous B-hCD94/hNKG2A mice and C57BL/6 mice, demonstrating that introduction of hCD94/hNKG2A in place of its mouse counterpart does not change the overall development, differentiation, or distribution of these cell types in spleen. Values are expressed as mean ± SEM.


Analysis of spleen leukocyte subpopulations in B-hCD94/hNKG2A mice

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Analysis of splenic T cell subpopulations by FACS
Splenocytes were isolated from female C57BL/6 and B-hCD94/hNKG2A mice (n=3, 6 weeks-old) and analyzed by flow cytometry for T cell subsets. (A) Representative FACS plots gated on TCRβ+ T cells and further analyzed. (B) Results of FACS analysis. Percentages of CD8+, CD4+, and Treg cells were similar in homozygous B-hCD94/hNKG2A and C57BL/6 mice, demonstrating that introduction of hCD94/hNKG2A in place of its mouse counterpart does not change the overall development, differentiation or distribution of these T cell subtypes in spleen. Values are expressed as mean ± SEM.


Analysis of lymph node leukocyte subpopulations in B-hCD94/hNKG2A mice

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Analysis of lymph node leukocyte subpopulations by FACS
Lymph node were isolated from female C57BL/6 and B-hCD94/hNKG2A mice (n=3, 6 weeks-old) and analyzed by flow cytometry to assess leukocyte subpopulations. (A) Representative FACS plots gated on single live CD45+ cells for further analysis. (B) Results of FACS analysis. Percentages of T, B, NK cells, monocytes/macrophages, and DC were similar in homozygous B-hCD94/hNKG2A mice and C57BL/6 mice, demonstrating that introduction of hCD94/hNKG2A in place of its mouse counterpart does not change the overall development, differentiation, or distribution of these cell types in lymph node. Values are expressed as mean ± SEM.


Analysis of lymph node leukocyte subpopulations in B-hCD94/hNKG2A mice


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Analysis of lymph node T cell subpopulations by FACS
Lymph node were isolated from female C57BL/6 and B-hCD94/hNKG2A mice (n=3, 6 weeks-old) and analyzed by flow cytometry for T cell subsets. (A) Representative FACS plots gated on TCRβ+ T cells and further analyzed. (B) Results of FACS analysis. Percentages of CD8+, CD4+, and Treg cells were similar in homozygous B-hCD94/hNKG2A and C57BL/6 mice, demonstrating that introduction of hCD94/hNKG2A in place of its mouse counterpart does not change the overall development, differentiation or distribution of these T cell subtypes in lymph node. Values are expressed as mean ± SEM.


Analysis of blood leukocyte subpopulations in B-hCD94/hNKG2A mice

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Analysis of blood leukocyte subpopulations by FACS
Blood were isolated from female C57BL/6 and B-hCD94/hNKG2A mice (n=3, 6 weeks-old) and analyzed by flow cytometry to assess leukocyte subpopulations. (A) Representative FACS plots gated on single live CD45+ cells for further analysis. (B) Results of FACS analysis. Percentages of T, B, NK cells, monocytes/macrophages, and DC were similar in homozygous B-hCD94/hNKG2A mice and C57BL/6 mice, demonstrating that introduction of hCD94/hNKG2A in place of its mouse counterpart does not change the overall development, differentiation, or distribution of these cell types in blood. Values are expressed as mean ± SEM.


Analysis of blood leukocyte subpopulations in B-hCD94/hNKG2A mice

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Analysis of blood T cell subpopulations by FACS
Blood were isolated from female C57BL/6 and B-hCD94/hNKG2A mice (n=3, 6 weeks-old) and analyzed by flow cytometry for T cell subsets. (A) Representative FACS plots gated on TCRβ+ T cells and further analyzed. (B) Results of FACS analysis. Percentages of CD8+, CD4+, and Treg cells were similar in homozygous B-hCD94/hNKG2A and C57BL/6 mice, demonstrating that introduction of hCD94/hNKG2A in place of its mouse counterpart does not change the overall development, differentiation or distribution of these T cell subtypes in blood. Values are expressed as mean ± SEM.


In vivo efficacy of anti-human NKG2A antibody

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Antitumor activity of anti-human NKG2A antibody in B-hCD94/hNKG2A mice. (A) Anti-human NKG2A antibody inhibited hHLA-E MC38 tumor growth in B-hCD94/hNKG2A mice. Murine colon cancer hHLA-E MC38 cells were subcutaneously implanted into homozygous B-hCD94/hNKG2A mice (female, 6-7 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, and treated with anti-hNKG2A antibody at doses and schedules in panel A. (B) Body weight changes during treatment. As shown in panel A, anti-human NKG2A antibody (monalizumab, in house) were efficacious in controlling tumor growth in B-hCD94/hNKG2A mice, demonstrating they provide a powerful preclinical model for in vivo evaluation of anti-human NKG2A antibody. Values are expressed as mean ± SEM.


In vivo efficacy of anti-human NKG2A antibody


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