HLA class I histocompatibility antigen A*02:01 (HLA-A*02:01)

HLA class I histocompatibility antigen A*02:01 is a specific allele of the human leukocyte antigen (HLA) system, which represents the human version of the major histocompatibility complex (MHC) (UniProt: P01892). It is a cell-surface glycoprotein that plays a fundamental role in the adaptive immune system by binding and presenting endogenous peptides, typically 8-10 amino acids in length, to CD8+ cytotoxic T cells (PubMed: 31515460). This particular allele is one of the most prevalent in Caucasian and other populations, making it a cornerstone for the development of HLA-restricted immunotherapies (NCI Dictionary). In oncology, the peptide-binding groove of HLA-A*02:01 is targeted by novel therapeutics such as bispecific T-cell engagers (e.g., Tebentafusp) and TCR-engineered T cells (e.g., Afamitresgene autoleucel), which are designed to recognize specific tumor-associated antigens only when presented by this specific HLA molecule (FDA: Kimmtrak; FDA: Tecelra). The therapeutic efficacy of these agents is strictly dependent on the patient's HLA-A*02:01 status and the presence of the target peptide within the groove. However, challenges include the potential for off-target toxicity if the drug recognizes similar peptides on healthy tissues or other HLA alleles, as well as the risk of tumor resistance through the loss of HLA expression (PubMed: 29439337).

Other names

HLA-A2HLA-A*0201MHC class I antigen A*02:01Human leukocyte antigen A*02:01Major histocompatibility complex, class I, A*02:01

Drugs targeting this molecule typically function as T-cell receptor (TCR) mimics, bispecific T-cell engagers, or TCR-engineered T-cell therapies that recognize a specific peptide-HLA complex, thereby recruiting and activating T cells to destroy target cells expressing that specific pMHC complex.