B6-hB2M&HLA-A2.1/mB2m KO Mice

Catalog Number: C001696

Strain Name: C57BL/6N;6JCya-Igs2^{em1(B2M/HLA-A2.1/H2-D1)}B2m^em2/Cya

Genetic Background: C57BL/6N;6JCya

Reproduction: Homozygous H11-hB2M&HLA-A2.1 mice x Homozygous mB2m KO mice

Strain Description

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 B6-hB2M&HLA-A2.1/mB2m KO mice are a humanized model obtained by mating H11-hB2M&HLA-A2.1 mice (Catalog Number: I001138) with 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.

Strain Strategy

• Gene editing strategy of H11-hB2M&HLA-A2.1 mice. The Mouse K2-K1 promoter- Kozak-HLA-A2.1 leader sequence-Human Mature B2M CDS-3xGGGGSChimeric-HLA-A2.1 (HLA-A2.1 alpha1 and alpha2 binding domains-H2-D1 alpha3, cytoplasmic and transmembrane domains)-H2-D1 3'sequence was integrated into the mouse H11 safe harbor site.

• Gene editing strategy for mB2m KO mice. Exons 2 to 3 of the endogenous mouse B2m gene were knocked out.
  
  

Applications

• 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.

References
[1]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.
[2]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.
[3]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.