Prostate-specific antigen peptide-major histocompatibility complex (PSA-pMHC)

Prostate-specific antigen (PSA) peptide-MHC complexes are cell-surface targets formed when intracellular PSA protein (KLK3) is proteolytically processed into short peptides and loaded onto Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 (PMID: 10449302). These complexes are presented on the surface of prostate cancer cells and professional antigen-presenting cells (APCs) that have cross-presented the antigen (PMID: 21149065). In the context of immunotherapy, these complexes act as specific ligands for T-cell receptors (TCRs) on cytotoxic CD8+ T-lymphocytes, triggering a targeted immune response against the tumor. Therapeutic approaches include viral vector vaccines like PROSTVAC-V/F, which aim to prime the immune system to recognize these specific peptide-MHC targets (PMID: 20406928). Additionally, engineered TCR-T cell therapies are being developed to bypass natural immune tolerance and provide high-affinity recognition of the PSA-pMHC ligand (PMID: 27535983). While PSA is a highly specific biomarker for prostate tissue, its expression in normal prostate cells and low levels in other tissues necessitate careful monitoring for on-target, off-tumor effects during clinical development.

Other names

PSA-HLA complexKLK3 peptide-MHCPSA-derived peptide-HLA-A2 complexProstate-specific antigen-MHC class I complexPSA-pHLA

Induction of cytotoxic T-lymphocyte (CTL) response against cells presenting PSA-derived peptides via MHC Class I molecules, leading to targeted cell lysis (PMID: 10449302).