HLA class I histocompatibility antigen, A-2 alpha chain (HLA-A*02:01) (HLA-A*02:01)

HLA-A*02:01 is a specific allele of the human leukocyte antigen (HLA) class I molecule, which plays a critical role in the adaptive immune system by presenting endogenous peptides to CD8+ cytotoxic T lymphocytes (UniProt: P01892). The peptide-binding groove of HLA-A*02:01 is a highly polymorphic region that anchors short peptides, typically 8-10 amino acids in length, derived from intracellular proteins such as viral or tumor-associated antigens (PubMed: 10605026). This presentation is essential for the surveillance and elimination of infected or malignant cells. In oncology, HLA-A*02:01 is the most common HLA allele in Caucasian populations, making it a primary target for the development of T-cell receptor (TCR)-based therapies and cancer vaccines (PubMed: 29103151). Therapeutic strategies often involve engineering TCRs or bispecific molecules, such as Tebentafusp, to recognize specific peptide-HLA-A*02:01 complexes (FDA: Kimmtrak). These drugs act by redirecting T cells to kill cells presenting specific antigens, such as gp100 or MAGE-A4, within the HLA-A*02:01 groove (PubMed: 35108502). However, the high specificity required for these interactions poses significant therapeutic challenges, as cross-reactivity with similar self-peptides in healthy tissues can lead to severe off-target toxicities (PubMed: 23833265). Additionally, the loss of HLA expression by tumor cells is a common mechanism of resistance to these therapies.

Other names

HLA-A2MHC class I antigen A*0201Human leukocyte antigen A2HLA-A*0201 MHC class I peptide-binding grooveHLA-A*02:01

Presentation of intracellularly derived antigenic peptides to CD8+ T-cells, enabling recognition by T-cell receptors (TCRs) or engineered TCR-mimetic therapeutics to induce targeted cell lysis.