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

The HLA class I histocompatibility antigen, A alpha chain (HLA-A) is a cell-surface glycoprotein belonging to the Major Histocompatibility Complex (MHC) class I, essential for the adaptive immune system [2, 3]. It functions as a specialized receptor that presents intracellularly derived peptide fragments (antigens) to the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, enabling the immune system to distinguish between healthy self-cells and those that are infected or malignant [5, 6, 11]. HLA-A is highly polymorphic, with thousands of allelic variants that dictate the specific repertoire of peptides an individual can present [5, 13]. In oncology, HLA-A is a critical therapeutic target; drugs like tebentafusp are bispecific molecules that redirect T cells to attack tumors by recognizing specific HLA-peptide complexes [1, 3, 15]. Conversely, many cancers evade immune surveillance by downregulating HLA-A expression or through mutations that disrupt the antigen-presentation pathway [12, 21]. Beyond cancer, specific HLA-A alleles serve as vital pharmacogenetic biomarkers for predicting severe drug hypersensitivity reactions and are fundamental in determining compatibility for organ and hematopoietic stem cell transplantation [3, 10, 16].

Other names

HLA-AHuman leukocyte antigen AMHC class I antigen AMajor histocompatibility complex class I ALeukocyte antigen class I-AHLA class I histocompatibility antigen, A-1 alpha chain

Drugs targeting HLA-A primarily function through T-cell redirection or MHC-restricted activation. Bispecific T-cell engagers (BiTEs) and ImmTACs (like tebentafusp) bind a specific HLA-A/peptide complex on tumor cells and CD3 on T cells to trigger cytotoxic activity [1, 3]. TCR-engineered T-cell therapies (TCR-T) involve modifying a patient's T cells to express a TCR that recognizes specific tumor antigens presented by HLA-A [5, 14, 16].