HLA class I histocompatibility antigen, A alpha chain (HLA-A*02) (HLA-A2)

HLA-A2 (specifically the HLA-A*02 allele) is a member of the Major Histocompatibility Complex (MHC) class I family, which is essential for the cellular immune response [1, 5]. It functions as a cell-surface receptor that presents intracellularly derived peptides, typically 8 to 10 amino acids in length, to CD8+ cytotoxic T cells [1, 5]. This presentation allows the immune system to monitor the internal health of cells, identifying those that are virally infected or have undergone malignant transformation [4, 5]. HLA-A2 is one of the most prevalent HLA alleles in Caucasian populations, making it a highly attractive target for "off-the-shelf" and personalized immunotherapies [2, 3]. Therapeutic interventions targeting HLA-A2 include T-cell receptor (TCR) engineered T-cells and bispecific TCR-mimetic molecules, which are designed to recognize specific tumor-associated peptides presented by the HLA-A2 molecule [2, 3]. For instance, tebentafusp is a bispecific protein that targets the gp100 peptide presented by HLA-A*02:01 to treat uveal melanoma [2]. Challenges in targeting HLA-A2 include the risk of cross-reactivity with other HLA alleles or self-peptides, which can lead to off-target toxicity and severe adverse events like cytokine release syndrome [3].

Other names

HLA-A*02MHC class I antigen A*2HLA-A2.1Human leukocyte antigen A2

Presentation of endogenous peptides to CD8+ T cells; targeted by TCR-engineered therapies or bispecific T-cell engagers that recognize specific peptide-HLA complexes.