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.

NKG mice are a type of severe immunodeficient mouse developed by Cyagen by deleting the Il2rg gene from the NOD-Scid strain. This strain lacks mature T, B, and NK cells, has reduced complement activity, and weak macrophage phagocytosis of human cells. As a result, NKG mice can efficiently engraft human hematopoietic stem cells (HSC), peripheral blood mononuclear cells (PBMC), patient-derived xenografts (PDX), or adult stem cells and tissues. In the field of immunology research, there are differences between humans and mice in terms of physiology and immune systems, so research conducted directly on mice cannot fully reflect the human situation. By transplanting human peripheral blood mononuclear cells (PBMC) or human hematopoietic stem cells (HSC) into immunodeficient mice, the mouse’s immune system is partially or completely replaced by the human immune system, allowing for the simulation of human immune system function in vivo. PBMC transplantation into NKG mice has the advantages of high immune reconstitution efficiency and fast speed. However, due to the mismatch between human immune cells and mouse MHC molecules, graft-versus-host disease (GvHD) occurs, where transplanted human immune cells (including T cells, B cells, and NK cells) attack mouse tissues, causing inflammation and tissue damage, ultimately leading to rapid death of the mouse. The B2M gene encodes β2-microglobulin, a serum protein that exists on the surface of almost all nucleated cells in conjunction with the major histocompatibility complex (MHC) class I heavy chain. It is an essential component for the transport of MHC class I proteins to the cell surface. Studies have shown that knocking out the B2m gene in immunodeficient mice can lead to a lack of MHC class I molecule expression, thereby reducing graft-versus-host disease (GvHD) ^[1-2]. In mice, MHC is commonly referred to as the H-2 complex. The H2-Ab1 gene encodes a part of the mouse MHC class II molecules. This complex is primarily present on the surface of antigen-presenting cells such as macrophages, dendritic cells, and B cells. It plays a crucial role in presenting fragments of foreign substances, such as bacteria or viruses, to helper T cells (CD4+ T cells). This antigen presentation is a fundamental step in initiating adaptive immune responses. Studies have shown that transplanting PBMCs into MHC II-deficient mice can prevent lethal graft-versus-host disease (GvHD) caused by CD4+ T cells ^[3-4]. NKG-B2m/H2-Ab1-DKO mice were obtained by crossing NKG B2m KO mice (catalog No. C001416) with NKG-H2-Ab1 KO mice (catalog No. C001498), which were effective in delaying the onset of graft-versus-host disease (GvHD). This model can be used for long-term studies of PBMC immune system reconstitution.