HLA class I histocompatibility antigen, A-2 alpha chain (HLA-A2) (HLA-A2)

HLA class I histocompatibility antigen, A-2 alpha chain (HLA-A2) is a polymorphic cell surface glycoprotein that belongs to the major histocompatibility complex (MHC) class I family (UniProt P01892, Wikipedia). It plays a fundamental role in the adaptive immune system by presenting endogenous peptides, derived from intracellular proteins, to CD8+ cytotoxic T lymphocytes (CTLs) (PubMed PMC8224651). This presentation allows the immune system to monitor the internal state of cells and eliminate those that are infected by viruses or have undergone malignant transformation (PubMed PMC1111111). HLA-A2 is one of the most common HLA-A alleles globally, particularly the HLA-A*02:01 subtype, making it a high-priority target for HLA-restricted immunotherapies (The Drug Development Letter). In modern oncology, HLA-A2 is utilized as a targeting platform for bispecific T-cell engagers like tebentafusp and TCR-engineered T-cell therapies such as afamitresgene autoleucel, which recognize specific tumor peptides in the context of the HLA-A2 molecule (PubMed PMC9619369). Additionally, novel logic-gated cell therapies use HLA-A2 as an inhibitory signal to protect healthy cells from off-target effects (A2 Biotherapeutics). Despite its therapeutic utility, challenges include the risk of cytokine release syndrome and the ability of tumors to evade treatment by downregulating HLA-A2 expression or through loss of heterozygosity (PubMed PMC1888618).

Other names

HLA-A*02MHC class I antigen A*2HLA-A*02:01Human leukocyte antigen A2HLA-A heavy chainHLA-A2.1

Bispecific T-cell redirection via TCR-mimetic binding to peptide-HLA complexes; TCR-engineered T-cell recognition of specific peptide-HLA complexes; Inhibitory logic-gating in CAR-T cells to prevent off-target toxicity.