Transgenic mouse models expressing human HLA-B57:01 and HLA-B15:02 molecules have emerged as invaluable tools for unraveling the intricacies of immune responses and hypersensitivity reactions. The major histocompatibility complex (MHC) encoded proteins play a pivotal role in the immune system by presenting peptide fragments to T lymphocytes, and HLA-B57:01 has been associated with severe hypersensitivity reactions triggered by abacavir, a widely used anti-retroviral drug. These transgenic mice, with HLA-B57:01 broadly expressed on their nucleated cells, provide a unique platform for investigating the underlying mechanisms of drug hypersensitivity, immune responses controlled by HLA-B57:01, and autoimmune pathology linked to this MHC molecule. Additionally, similar models expressing HLA-B15:02 facilitate the study of hypersensitivity reactions related to carbamazepine. Notably, these models represent a significant breakthrough, as prior to this research, animal models for exploring immune responses based on HLA-B57:01 and HLA-B15:02 had not been reported, and specific HLA-B*57:01 restricted immune responses have been observed, offering new avenues for research in immunology and drug safety.