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

HLA class I histocompatibility antigen, A alpha chain (specifically the HLA-A*02:01 allele) is a critical component of the human major histocompatibility complex (MHC) class I system (UniProt P04439, Wikipedia). It functions as a cell-surface receptor that presents intracellularly processed peptides to CD8+ cytotoxic T cells, thereby facilitating the immune surveillance of viral infections and malignant transformations (UniProt, PubChem). HLA-A*02:01 is one of the most prevalent alleles in human populations, particularly among Caucasians, making it a primary focus for the development of TCR-based immunotherapies (NCI, The Drug Development Letter). Therapeutic strategies targeting this molecule include TCR-engineered T cells (TCR-T) and bispecific T-cell engagers (ImmTACs) that recognize specific tumor-associated antigens, such as gp100 or MAGE-A4, when presented by HLA-A*02:01 (PubMed, PMC). For instance, tebentafusp is an approved bispecific protein that targets the gp100 peptide-HLA complex in uveal melanoma (The Drug Development Letter). Beyond its role as a positive target, HLA-A*02:01 is also utilized in logic-gated cell therapies as an inhibitory signal to protect healthy cells from off-target attack (Molecular Therapy — Oncolytics). However, the efficacy of these treatments can be limited by tumor-mediated loss of the HLA-A*02:01 allele, a process known as loss of heterozygosity (LOH).

Other names

Human leukocyte antigen A*02:01MHC class I antigen A*02:01HLA-A2HLA-A*0201MHC class I HLA-A proteinHLA class I histocompatibility antigen, A-1 alpha chain

Presentation of intracellularly derived peptides to T-cell receptors (TCRs) or TCR-mimetic bispecific molecules to trigger immune-mediated cell lysis; also serves as an inhibitory ligand in logic-gated cell therapies to prevent off-target activity.