Human leukocyte antigen A*02:17 (HLA-A*02:17)

HLA-A*02:17 is a specific allele of the Human Leukocyte Antigen (HLA) class I A gene, belonging to the widely studied HLA-A*02 (A2) serotype and supertype. As a major histocompatibility complex (MHC) class I molecule, its primary biological function is to present endogenous peptide fragments, derived from intracellular proteins, to CD8+ cytotoxic T lymphocytes (CTLs). This process is essential for immune surveillance, allowing the immune system to detect and eliminate cells that are infected by viruses or have undergone malignant transformation. HLA-A*02:17 is a relatively low-frequency allele but is clinically significant in the context of personalized immunotherapy, where it serves as a restriction element for T-cell receptor (TCR)-based therapies and cancer vaccines. In oncology, HLA-A*02:17 is targeted indirectly through TCR-T cell therapies and bispecific T-cell engagers (such as tebentafusp) that recognize specific tumor-associated antigens like PRAME or gp100 presented by HLA-A*02 molecules. Additionally, it is utilized in novel "logic-gated" CAR-T cell strategies, such as the Tmod platform, where the HLA-A*02 molecule itself acts as an inhibitory signal to protect healthy cells from off-tumor attack in patients whose tumors have lost the allele through loss of heterozygosity (LOH). Beyond cancer, HLA-A*02:17 has been associated with certain autoimmune conditions, such as acquired idiopathic neutropenia and aplastic anemia, where aberrant antigen presentation may trigger the immune-mediated destruction of hematopoietic cells.

Other names

HLA-A2MHC class I antigen A*02:17HLA-A*0217HLA-A*02:17:01GMajor histocompatibility complex, class I, A (allele A*02:17)

Presentation of intracellularly derived antigenic peptides to CD8+ T-cell receptors (TCRs) and serving as an inhibitory target for logic-gated chimeric antigen receptor (CAR) T-cell therapies.