Human leukocyte antigen A2 (HLA-A2) (HLA-A2)

Human leukocyte antigen A2 (HLA-A2) is a major histocompatibility complex (MHC) class I molecule that plays a pivotal role in the adaptive immune system by presenting intracellularly derived peptides to CD8+ cytotoxic T lymphocytes (PubMed: 8524181). The peptide-binding groove of HLA-A2 is a highly polymorphic region that anchors short amino acid sequences, typically 8-10 residues in length, including those derived from tumor-associated antigens (TAAs) such as gp100, MAGE-A4, and NY-ESO-1 (Wikipedia: HLA-A*02). In oncology, this complex serves as a critical therapeutic target for T-cell receptor (TCR)-based therapies, bispecific T-cell engagers like tebentafusp, and cancer vaccines, as it allows the immune system to recognize and eliminate malignant cells expressing specific intracellular proteins (PubMed: 36191584). HLA-A2 is the most prevalent MHC class I allele in Caucasian populations, making it a primary focus for personalized immunotherapy and a key requirement for patient eligibility in many clinical trials (PubMed: 22421941). However, therapeutic efficacy can be limited by tumor-mediated downregulation of HLA expression or loss of heterozygosity (LOH), which allows cancer cells to evade immune detection (PMC: 9745325). Additionally, the risk of off-target toxicity exists if the targeted peptide-HLA complex is mimicked by similar sequences in healthy tissues, necessitating rigorous specificity testing for HLA-A2-targeted agents (PMC: 10720114).

Other names

HLA-A*02MHC class I antigen A*02Major histocompatibility complex, class I, AHLA-A2-peptide complexpMHC complex

Presentation of intracellularly derived tumor-associated antigen (TAA) peptides to CD8+ cytotoxic T lymphocytes (CTLs) via the T-cell receptor (TCR) or TCR-mimic molecules to induce tumor cell lysis.