HLA class I antigen alpha chain A*02:01 (HLA-A*02:01)

HLA class I antigen alpha chain A*02:01 is a specific protein variant of the Human Leukocyte Antigen A (HLA-A) gene, belonging to the Major Histocompatibility Complex (MHC) class I family (UniProt). It is expressed on the surface of nearly all nucleated cells and functions to present short, intracellularly derived peptides to CD8+ cytotoxic T cells, thereby facilitating the detection of viral infections and malignant transformations (NIH). As one of the most prevalent HLA alleles in Western populations, it has become a cornerstone of precision oncology, serving as the restrictive element for numerous T-cell receptor (TCR)-based therapies and cancer vaccines (NCI, drugdevletter.com). Therapeutic agents such as tebentafusp and afamitresgene autoleucel are designed to specifically recognize peptide-HLA-A*02:01 complexes, enabling the immune system to target and eliminate tumor cells (FDA, NIH). However, the high degree of polymorphism in the HLA system means that these therapies are only effective in patients carrying this specific allele, highlighting the importance of HLA genotyping in clinical practice (JAMA Network Open). Safety concerns associated with targeting this molecule include cytokine release syndrome and potential off-target effects if the presented peptide is found in healthy tissues (NIH).

Other names

HLA-A2MHC class I antigen A*02:01Human leukocyte antigen A*02:01HLA-A*0201HLA class I histocompatibility antigen, A alpha chain

Drugs targeting this molecule typically function by redirecting T-cell activity toward cells presenting specific antigens in the context of the HLA-A*02:01 complex. This is achieved through bispecific fusion proteins (e.g., tebentafusp) that bind both the peptide-HLA complex and the T-cell receptor/CD3, or through adoptive cell therapies (e.g., afamitresgene autoleucel) where T cells are engineered with TCRs specific to the peptide-HLA-A*02:01 target (NIH).