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

HLA class I histocompatibility antigen, A-2 alpha chain (HLA-A2) is a critical component of the human major histocompatibility complex (MHC) class I system, primarily responsible for presenting endogenous peptides to CD8+ cytotoxic T cells [1, 5]. It forms a heterodimer with beta-2-microglobulin to display fragments of intracellular proteins on the cell surface, allowing the immune system to monitor for viral infections or malignant transformations [1, 4]. HLA-A2 is one of the most common HLA alleles in Caucasian populations, making it a primary target for the development of HLA-restricted immunotherapies [5, 8]. In oncology, several advanced therapeutics, such as bispecific T-cell engagers and TCR-engineered T cells, are designed to recognize specific peptide-HLA-A2 complexes on tumor cells [4, 7]. For instance, tebentafusp targets the gp100 peptide presented by HLA-A*02:01, while afamitresgene autoleucel targets MAGE-A4 in the context of this specific HLA molecule [2, 3]. Despite its therapeutic utility, tumors often evade immune detection by downregulating or losing HLA-A2 expression, which poses a significant challenge to the sustained efficacy of these treatments [8, 16].

Other names

HLA-A*02MHC class I antigen A*2Human leukocyte antigen A2HLA class I histocompatibility antigen, A-2 alpha chainHLA-A2.1

The HLA-A2 alpha chain presents specific intracellularly derived peptide antigens to the T-cell receptors (TCRs) of CD8+ T cells; modern drugs target this molecule by using engineered TCRs or bispecific antibodies that bind the unique peptide-HLA complex to trigger immune-mediated cell death.