H11-hB2M & HLA-A24 Mouse

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.