Human leukocyte antigen A3 (HLA-A3)

Human leukocyte antigen A3 (HLA-A3) is a major histocompatibility complex (MHC) class I molecule encoded by the HLA-A*03 allele group [1]. It is expressed on the surface of almost all nucleated cells and plays a fundamental role in the adaptive immune system by presenting endogenous peptides to CD8+ cytotoxic T lymphocytes [2]. This presentation allows the immune system to monitor the intracellular environment and eliminate cells that are virally infected or have undergone malignant transformation [2]. HLA-A3 is clinically significant as a genetic risk factor for several autoimmune and metabolic disorders, most notably Multiple Sclerosis and Hereditary Hemochromatosis [1, 5]. In oncology, HLA-A3 is a key target for HLA-restricted therapies, including peptide-based vaccines like Nelipepimut-S and GP2, as well as TCR-engineered T cell therapies, which are designed to recognize specific tumor antigens in the context of this allele [3]. However, recent clinical evidence suggests that the presence of the HLA-A*03 allele may be associated with a diminished response to immune checkpoint inhibitors across various cancers [4]. References: [1] Wikipedia, HLA-A3; [2] NIH, MHC Class I; [3] Frontiers in Oncology, Breast Cancer Vaccines; [4] NIH/PubMed, HLA-A*03 and ICI Response; [5] ResearchGate, HLA-A3 and Multiple Sclerosis.

Other names

HLA-A*03HLA-A*03:01HLA-A*03:02MHC class I antigen A*03HLA class I histocompatibility antigen, A-3 alpha chain

HLA-A3 acts as a scaffold for presenting specific antigenic peptides to T-cell receptors (TCRs) on CD8+ T cells. Therapeutic vaccines and TCR-T therapies leverage this by introducing peptides or engineered receptors that specifically recognize the HLA-A3-peptide complex, triggering targeted cell lysis.