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

The HLA-A*02:01-presented tumor-associated peptide complex is a pivotal target in precision oncology, consisting of a specific Major Histocompatibility Complex (MHC) Class I molecule and a processed intracellular protein fragment. HLA-A*02:01 is one of the most prevalent Class I alleles in human populations and serves to present these peptides on the cell surface for surveillance by CD8+ cytotoxic T lymphocytes (UniProt: P01892). In malignant cells, these complexes often display peptides derived from overexpressed tumor-associated antigens or mutated neoantigens, providing a unique signature for immune discrimination. Modern therapeutic modalities, such as TCR-engineered T-cells (e.g., Afamitresgene autoleucel) and TCR-bispecific engagers (e.g., Tebentafusp), are engineered to recognize these specific peptide-MHC configurations with high affinity and specificity (FDA: Tecelra, Kimmtrak). This targeting strategy allows the immune system to bypass natural tolerance and potently destroy tumor cells that do not express traditional surface markers. However, the clinical success of these therapies is contingent upon the density of the complex on the tumor surface and the avoidance of cross-reactivity with similar peptide sequences found in vital organs (PubMed: PMID 34161771).

Other names

HLA-A*02:01-presented tumor-associated peptide complexHLA-A2-restricted peptide-MHC complexpMHC complexHLA-A*02:01-antigen complexMHC class I-peptide complex

T-cell redirection and activation via T-cell receptor (TCR) or TCR-mimetic binding to the specific peptide-MHC complex on the cell surface.