Human leukocyte antigen class I A-2 alpha chain (HLA-A*02:01)

The Human leukocyte antigen class I A-2 alpha chain, commonly known as HLA-A*02:01, is a critical component of the major histocompatibility complex (MHC) class I system. It functions as a cell-surface receptor that presents intracellularly derived peptides, typically 8-10 amino acids in length, to CD8+ cytotoxic T-lymphocytes. This presentation is essential for the immune system to monitor for viral infections and malignant transformations within cells. HLA-A*02:01 is one of the most prevalent HLA alleles in Caucasian populations, making it a primary focus for the development of HLA-restricted immunotherapies. In the context of disease, HLA-A*02:01 plays a dual role; it is involved in the presentation of tumor-associated antigens like gp100 and MAGE-A4, but it is also associated with susceptibility to certain autoimmune conditions and transplant rejection. Therapeutic strategies targeting this molecule include bispecific T-cell engagers (BiTEs) and T-cell receptor (TCR) engineered T-cell therapies, which are designed to recognize specific peptide-HLA complexes on cancer cells. For example, tebentafusp is a bispecific protein that redirects T cells to kill uveal melanoma cells presenting the gp100 peptide via HLA-A*02:01. However, the use of these therapies is limited to patients who carry this specific allele, raising concerns about equitable access across different ethnic groups with lower allele frequencies.

Other names

HLA-A2HLA-A*0201MHC class I antigen A*2HLA-A2.1HLA-A*02:01:01:01HLA-A*02

The molecule functions by presenting intracellularly processed peptides to CD8+ cytotoxic T-lymphocytes. Therapeutic agents such as bispecific T-cell engagers (e.g., tebentafusp) or TCR-engineered T cells (e.g., afamitresgene autoleucel) are designed to recognize specific peptide-HLA complexes, thereby redirecting the immune system to eliminate cells expressing target antigens like gp100 or MAGE-A4.