Cluster of Differentiation 3 (CD3) is a protein complex that functions as a co-receptor on T cells, playing a critical role in the activation of cytotoxic T lymphocytes (CTLs) and helper T cells (THs). CD3 comprises five transmembrane polypeptide chains—γ, δ, ε, ζ, and η—each contributing to the structural integrity and signaling capacity of the complex. The transmembrane domains of CD3 form salt bridges with the transmembrane regions of the T cell receptor (TCR) α and β chains, assembling into the TCR-CD3 complex that mediates antigen recognition by T cells ^[1-2]. Upon antigen engagement by the TCR, activation signals are transduced intracellularly via CD3. CD3 is expressed with high specificity throughout all stages of T cell development and is therefore widely utilized as an immunohistochemical marker for T cell identification. Moreover, CD3 is present in nearly all T cell lymphomas and leukemias, enabling differential diagnosis from morphologically similar B cell and myeloid malignancies. Given its pivotal role in T cell activation and antigen recognition, CD3 has emerged as a key therapeutic target in immunosuppressive strategies for type 1 diabetes and other autoimmune disorders ^[3].

The B2M gene encodes β2-microglobulin, a serum protein that associates with the heavy chain of major histocompatibility complex (MHC) class I molecules and is essential for their surface expression on virtually all nucleated cells. Human leukocyte antigens (HLAs), also referred to as MHC molecules, are cell-surface proteins responsible for antigen presentation. The HLA system comprises class I, class II, and class III molecules. HLA class I molecules—including HLA-A, HLA-B, and HLA-C—primarily present antigens to CD8⁺ T cells and are central to immune surveillance. Through HLA class I–mediated antigen presentation, the immune system can detect aberrant peptides and initiate targeted cytotoxic responses for immune clearance. HLA-A2.1 is a subtype of HLA class I and represents one of the most prevalent HLA alleles worldwide.

The B6-hCD3/H11-hB2M&HLA-A2.1 mouse model is generated by crossing B6-hCD3 mice (catalog no. C001325) with H11-hB2M&HLA-A2.1 mice (catalog no. I001138). These mice co-express human CD3, human β2-microglobulin, and HLA-A0201 proteins in vivo. This model enables mechanistic investigation of T cell activation, antigen recognition, and antigen presentation, and serves as a versatile platform for evaluating immunosuppressive therapies in autoimmune diseases, studying human viral infections, and developing and testing novel viral vaccines.