Prostate-specific membrane antigen (PSMA) HLA-A*02:01-restricted peptide-MHC complex (HLA-A2/PSMA complex)

The Prostate-specific membrane antigen (PSMA) HLA-A*02:01-restricted peptide-MHC complex consists of specific peptide fragments derived from the PSMA protein (also known as Folate Hydrolase 1) presented on the cell surface by the Human Leukocyte Antigen A2 molecule. PSMA is a type II transmembrane glycoprotein that is significantly overexpressed in nearly all stages of prostate cancer, making it a premier target for diagnostic imaging and therapy (UniProt Q04609). While many therapies target the extracellular domain of the intact PSMA protein, HLA-restricted epitopes allow for the targeting of tumor cells via the T-cell receptor (TCR) pathway, enabling the use of TCR-engineered T cells (TCR-T) and peptide vaccines (PMID: 10543458). These epitopes, such as PSMA 4-12 or PSMA 711-719, are processed intracellularly and presented to CD8+ cytotoxic T lymphocytes, which can then trigger apoptosis in the malignant cells (PMID: 31515463). This target is particularly valuable for patients who are HLA-A2 positive, providing a mechanism to engage the cellular immune system against prostate tumors. Therapeutic development in this area focuses on overcoming the immunosuppressive tumor microenvironment and potential off-target effects in tissues like the salivary glands and kidneys where PSMA is also expressed.

Other names

HLA-A2-restricted PSMA epitopesPSMA-derived HLA-A2 epitopesFOLH1-HLA-A*02:01 complexPSMA pMHCProstate-specific membrane antigen HLA-A2 complex

Induction of T-cell mediated cytotoxicity through specific recognition of the peptide-MHC complex by the T-cell receptor (TCR) on CD8+ cytotoxic T lymphocytes.