H11-hB2M&HLA-A24 Mice

Catalog Number: I001137

Strain Name: C57BL/6NCya-Igs2em1(B2M/HLA-A24/H2-K1)/Cya

Genetic Background: C57BL/6NCya

 

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-A24 (A24) is a human leukocyte antigen of the HLA-A serotype group, with its alpha chain encoded by the HLA-A*24 allele and its beta chain encoded by the B2M gene. The H11-hB2M&HLA-A24 mouse model is constructed by integrating the chimeric H2-K1 HLA-A24 gene into the H11 safe harbor locus of mice using gene editing technology. This humanized model can be used to identify viral peptides that express HLA-A24 binding sequences.

Strain Strategy


Figure 1. Gene editing strategy of H11-hB2M&HLA-A24 mice. The Mouse K2-K1 promoter-Kozak-HLA-A2.1 leader sequence-Human Mature B2M CDS-3xGGGGS Chimeric HLA-A24 (HLA-A24 alpha1 and alpha2 binding domains-H2-K1 alpha3, cytoplasmic and transmembrane domains)-H2-K1 3’sequence was integrated into the mouse H11 safe harbor site.

Application

  • Research on human viral infectious diseases;
  • Development and testing of novel viral vaccines;
  • Safety and immunogenicity testing of drugs and vaccines;
  • Research on oncology and autoimmune diseases;
  • Study of the interactions between human immune cells and pathogens;
  • Research on homologous tumor transplantation (Syngeneic).

 

Validation Data

1. Mice successfully express human B2M protein and HLA-A2402 protein.

Figure 2. Human HLA-A2402 protein and human B2M protein expression in the spleen and peripheral blood (PB) of H11-hB2M&HLA-A24 mice. The results show that the H11-hB2M&HLA-A24 mice successfully express human HLA-A2402 protein and human B2M protein in peripheral blood and spleen.

2. Detection of splenic immune cells (T, B, and NK Cells)

Figure 3. Proportions of T, B, and NK cells in the spleen of H11-hB2M&HLA-A24 mice. The results show that, compared to wild-type mice (WT), there are no significant differences in the proportions of T, B, and NK cells in the spleen of H11-hB2M&HLA-A24 mice.

3. Detection of peripheral blood immune cells (T, B, and NK Cells)


Figure 4. Proportions of T, B, and NK cells in the peripheral blood of H11-hB2M&HLA-A24 mice. The results show that, compared to wild-type mice (WT), there are no significant differences in the proportions of T, B, and NK cells in the peripheral blood of H11-hB2M&HLA-A24 mice.

 

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.