The NCG-HLA-A2.1 mouse is an advanced immunodeficient model designed to support human T cell development and function through the expression of the human HLA-A*02:01 gene on the NCG background. HLA-A2.1 is a key human MHC class I molecule that plays a central role in antigen presentation and CD8⁺ cytotoxic T lymphocyte (CTL) recognition.

This model carries a chimeric HLA-A2.1/H2-Kb transgene, in which the human α1 and α2 domains (responsible for antigen binding) are fused to the murine α3, transmembrane, and cytoplasmic domains, allowing efficient interaction with murine CD8 during T cell development. However, in the NCG-HLA-A2.1 strain, the α3 domain is humanized, making the interaction fully compatible with human CD8⁺ T cells, thereby enhancing the maturation and functionality of human T cells following CD34⁺ hematopoietic stem cell transplantation.