Human serum albumin-derived peptide-major histocompatibility complex (HSA-pMHC)

The Human serum albumin (HSA)-derived peptide-MHC complex consists of a specific fragment of the HSA protein presented on the surface of nucleated cells by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01. As HSA is the most abundant protein in human plasma, its derived peptides are ubiquitous self-antigens to which the immune system is normally tolerant. In the context of modern drug development, this complex is not a therapeutic target but rather a critical 'negative target' or off-target used to screen the specificity of T-cell receptor (TCR)-engineered T cells and TCR-like antibodies. Cross-reactivity with this complex can lead to catastrophic systemic toxicity, as seen in historical clinical trials where engineered T cells recognized similar self-peptides. Additionally, the complex plays a role in drug-induced hypersensitivity, where certain drugs (haptens) bind to HSA, creating neoantigens that trigger pathogenic T-cell responses.

Other names

HLA-A*02:01/HSA(443-451) complexAlbumin-derived peptide-MHC complexHSA-pMHC complexSelf-peptide-MHC complex

Not applicable as a therapeutic target; primarily serves as a negative control or off-target in drug development.