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

HLA class I histocompatibility antigen A2 (HLA-A2) is a specific allele group of the Human Leukocyte Antigen A (HLA-A) gene, encoding a major histocompatibility complex (MHC) class I molecule. It is expressed on the surface of nearly all nucleated cells and plays a fundamental role in the adaptive immune system by presenting endogenous peptides to CD8+ cytotoxic T lymphocytes (UniProt: P04439). This mechanism allows the immune system to detect and eliminate cells harboring intracellular pathogens or expressing mutated neoantigens associated with cancer (PubMed: 31435457). HLA-A2 is one of the most prevalent HLA alleles in human populations, particularly in Caucasians, making it a primary focus for the development of antigen-specific immunotherapies. In drug development, HLA-A2 serves as a critical restriction element for T-cell receptor (TCR)-based therapies, such as Tebentafusp and Afamitresgene autoleucel, which are designed to recognize specific tumor peptides only when presented by this specific HLA molecule (FDA: Tebentafusp Label). Consequently, patient selection for these therapies requires molecular testing to confirm the presence of the HLA-A*02:01 genotype.

Other names

HLA-A*02MHC class I antigen A*2HLA-A2.1Human leukocyte antigen A2Major histocompatibility complex class I A2

Presents intracellularly derived peptide antigens to CD8+ T-cell receptors (TCRs) to initiate a cytotoxic immune response against infected or malignant cells.