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H11-hB2M&HLA-A2.1/B2m-KO Mouse
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H11-hB2M&HLA-A2.1/B2m-KO Mouse
제품명
H11-hB2M&HLA-A2.1/B2m-KO Mouse
제품 ID
C001696
품종 계통
C57BL/6N;6JCya-Igs2em1(B2M/HLA-A2.1/H2-D1)B2mem2/Cya
Backgroud
C57BL/6N;6JCya
상태
이 마우스 계통을 논문에서 사용할 경우, “H11-hB2M&HLA-A2.1/B2m-KO Mouse (카탈로그 번호 C001696)은 Cyagen에서 구입하였습니다.”라고 명시해 주시기 바랍니다.
Other Target Humanized Mouse Models
구매 가능한 제품 종류
연령
Genotype
성별
수량
표준 제공 조건은 최소 3마리의 이형접합(heterozygous) 보균자를 보장합니다. 동형접합(homozygous) 보균자 및/또는 특정 성별에 대한 브리딩 서비스도 제공됩니다.
가격 문의
Other Target Humanized Mouse Models
기본 정보
검증 데이터
관련 자료
기본 정보
유전자 별칭
Ly-m11, beta2m, beta2-m, HLAA, IMD43
염색체
Chr 2, Chr 6, Chr 15
MGI ID
Datasheet
품종 계통 설명
The B2M gene encodes beta-2 microglobulin, a serum protein on the surface of nearly all nucleated cells along with the major histocompatibility complex (MHC) class I heavy chain. It is an essential component for transporting MHC class I proteins to the cell surface. Human leukocyte antigen (HLA), or the major histocompatibility complex (MHC), is a group of protein molecules on the surface of antigen-presenting cells responsible for antigen presentation. HLA mainly includes HLA class I, HLA class II, and HLA class III. HLA class I molecules (such as HLA-A, HLA-B, and HLA-C) primarily present antigens to CD8+ T cells and play a central role in the immune system. Through antigen presentation by HLA class I, the body can effectively recognize abnormal peptides, triggering targeted immune responses for immune clearance. Studies have shown that peptide vaccines composed of covalently linked minimal cytotoxic T lymphocyte (CTL) and T helper cell (TH) epitopes have significant effects in inducing cellular immune responses [1]. Due to species differences between mice and humans, and the varying ability of different HLA molecule subtypes to present different antigens, mouse-derived HLA cannot effectively simulate the immune response of human HLA subtypes. Therefore, constructing mice carrying human HLA genes helps to advance the study of HLA-restricted cytotoxic responses, such as identifying immunodominant HLA-restricted CTL epitopes and optimizing DNA vaccine constructs for human use [2-3].
HLA-A2.1 is a subtype of class I HLA and is one of the most common HLA subtypes worldwide. HLA-A2.1 plays an important role in the immune system, especially in the presentation of antigens such as viruses, bacteria, and parasites to cytotoxic T cells (CD8+ T cells). This presentation process is essential for the immune response of the human body to a variety of pathogens, particularly in the response to human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In addition, HLA-A2.1 is also involved in the immune response to cancer cells, further emphasizing its importance in the human immune system.
The H11-hB2M&HLA-A2.1/B2m-KO mice are a humanized model obtained by mating H11-hB2M&HLA-A2.1 mice (Catalog Number: I001138) with the B2m gene knockout mouse model (Catalog Number: S-KO-19919). While knocking out the mouse B2m gene, the chimeric H2-K1 HLA-A2.1 gene is integrated into the H11 safe harbor locus, which may be able to recapitulate the immune response of the human HLA-A*0201 (MHCI) subtype. This model can play an important role in studying the determinants of HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs) and the development of potential viral vaccines and helps research the human immune response to a variety of antigens.
Reference
La Rosa C, Wang Z, Brewer JC, Lacey SF, Villacres MC, Sharan R, Krishnan R, Crooks M, Markel S, Maas R, Diamond DJ. Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice. Blood. 2002 Nov 15;100(10):3681-9.
Gotoh M, Takasu H, Harada K, Yamaoka T. Development of HLA-A2402/K(b) transgenic mice. Int J Cancer. 2002 Aug 10;100(5):565-70.
Boucherma R, Kridane-Miledi H, Bouziat R, Rasmussen M, Gatard T, Langa-Vives F, Lemercier B, Lim A, Bérard M, Benmohamed L, Buus S, Rooke R, Lemonnier FA. HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 monochain transgenic/H-2 class I null mice: novel versatile preclinical models of human T cell responses. J Immunol. 2013 Jul 15;191(2):583-93.
변형 전략

Figure 1. Strategy for generating H11-hB2M&HLA-A2.1 mice.A synthetic gene expression cassette—“Mouse K2-K1 promoter–Kozak–HLA-A2.1 leader sequence–Human Mature B2M CDS–3×GGGGS linker–Chimeric HLA-A2.1 (HLA-A2.1 α1 and α2 binding domains fused to H2-D1 α3, cytoplasmic, and transmembrane domains)–H2-D1 3′ sequence”—was integrated into the murine H11 safe harbor locus using genome editing technologies.

Figure 2. Gene editing strategy for mB2m KO mice.Exons 2 to 3 of the endogenous mouse B2m gene were knocked out.
응용 분야
Development and testing of novel viral vaccines;
Testing of drug and vaccine safety and immunogenicity;
Research on oncology and autoimmune diseases;
Research on the interaction mechanism between human immune cells and pathogens;
Research on allogeneic tumor transplantation.
검증 데이터
1. T Cell Subset Analysis
Peripheral blood and spleens were harvested from 6-week-old male mice. Flow cytometry was used to quantify CD3⁺, CD3⁺CD4⁺, and CD3⁺CD8⁺ T cell frequencies. Results showed no significant differences between H11-hB2M-HLA-A2.1 and wild-type mice. Endogenous mouse B2m gene knockout resulted in a significant decrease in CD8⁺ T cell proportions.

Figure 3. T cell proportions in peripheral blood and spleens of H11-hB2M&HLA-A2.1/B2m-KO, H11-hB2M-HLA-A2.1, and wild-type mice (6-week-old male).
2. Functional Antigen Presentation Validation
Bone marrow cells were isolated from H11-hB2M&HLA-A2.1/B2m-KO and wild-type (WT) mice and differentiated in vitro into bone marrow-derived dendritic cells (BMDCs). Following pulsing with the NY-ESO-1157-165 peptide (SLLMWITQC), BMDCs were co-cultured with Jurkat reporter cells stably expressing human CD8, a NY-ESO-1-specific TCR, and a TCR signaling-driven EGFP reporter. EGFP expression was quantified via flow cytometry to evaluate the functional presentation of HLA-A2/pMHC complexes.
Significant EGFP positivity and high fluorescence intensity were observed in Jurkat reporter cells only when co-cultured with peptide-pulsed BMDCs derived from H11-hB2M&HLA-A2.1/B2m-KO mice. Conversely, WT BMDCs failed to induce significant TCR activation despite identical peptide loading. Furthermore, no notable fluorescence was detected in control groups treated with the peptide alone or lacking the HLA-A2 background, ruling out direct peptide stimulation or non-specific activation. These findings demonstrate that BMDCs from H11-hB2M&HLA-A2.1/B2m-KO mice can efficiently load and functionally present HLA-A2-restricted peptide antigens to specifically activate the CD8⁺ TCR signaling pathway, confirming that the model possesses intact human HLA-A2 antigen presentation capabilities.

Figure 4. Validation of functional HLA-A2 antigen presentation by BMDCs derived from H11-hB2M&HLA-A2.1/B2m-KO mice.
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