Human leukocyte antigen A*02:01 peptide-major histocompatibility complex (HLA-A*02:01 pMHC) (HLA-A*02:01 pMHC)

The Human leukocyte antigen A*02:01 (HLA-A*02:01) peptide-major histocompatibility complex (pMHC) is a cell-surface molecule essential for the adaptive immune system's ability to monitor intracellular health. It consists of a polymorphic alpha heavy chain, a non-covalently associated beta-2 microglobulin (B2M) subunit, and a short antigenic peptide, typically 8 to 10 amino acids in length, derived from proteasomal degradation of cellular proteins (UniProt: P01892). HLA-A*02:01 is one of the most prevalent MHC class I alleles in human populations, particularly among Caucasians, making it a cornerstone for the development of immunotherapies. In oncology, these complexes present tumor-associated antigens (TAAs) or neoantigens that can be specifically recognized by T-cell receptors (TCRs). Modern therapeutic interventions, such as TCR-engineered T-cells (TCR-T) and Immune mobilizing monoclonal TCRs Against Cancer (ImmTACs), are engineered to bind these specific pMHC targets to trigger potent T-cell-mediated cytotoxicity against malignant cells (PubMed: 32029624). However, the high degree of similarity between certain tumor-derived peptides and self-peptides presented on healthy tissues poses a significant risk of off-target toxicity, necessitating rigorous specificity screening during drug development.

Other names

HLA-A2HLA-A*0201MHC class I antigen A*02:01pMHC complex

T-cell receptor (TCR) mediated recognition and subsequent T-cell activation and redirection