Human leukocyte antigen A (HLA-A) (HLA-A)

Human leukocyte antigen A (HLA-A) is a critical component of the Major Histocompatibility Complex (MHC) class I system, serving as a cell-surface receptor that presents intracellular peptides to CD8+ cytotoxic T cells [UniProt, P04439]. It consists of a highly polymorphic alpha heavy chain non-covalently linked to beta-2 microglobulin, forming a groove that binds peptides typically 8-10 amino acids in length [NCBI, Gene ID 3105]. By displaying a representative sample of the cellular proteome, HLA-A enables the immune system to distinguish between healthy self-cells and those harboring viral infections or oncogenic mutations [PubMed, 11160674]. In modern oncology, HLA-A is a foundational target for T-cell receptor (TCR) engineered therapies and bispecific T-cell engagers, which are designed to recognize specific tumor antigens in the context of particular HLA-A alleles, most notably HLA-A*02:01 [FDA, Tebentafusp Label]. However, the effectiveness of these therapies is often limited by tumor-mediated immune evasion strategies, such as the downregulation of HLA-A expression or the loss of heterozygosity at the HLA locus [PubMed, 29233918]. Beyond its role in cancer and infection, HLA-A is a primary determinant of histocompatibility in organ and bone marrow transplantation, where mismatches can lead to severe graft rejection or graft-versus-host disease [StatPearls, NBK541011].

Other names

MHC class I antigen AHLA class I antigen AMajor histocompatibility complex, class I, AHLA-A heavy chain

HLA-A molecules function as restriction elements that present processed intracellular peptide antigens to the T-cell receptors (TCRs) of CD8+ T cells, thereby initiating an adaptive immune response against infected or malignant cells [UniProt, P04439].