Prostate-specific antigen peptide–Major Histocompatibility Complex (PSA-pMHC)

The Prostate-specific antigen peptide–Major Histocompatibility Complex (PSA-pMHC) is a molecular assembly presented on the surface of prostate cells and antigen-presenting cells (APCs). It consists of a short peptide fragment derived from the prostate-specific antigen (PSA, also known as KLK3) bound within the groove of a Major Histocompatibility Complex (MHC) molecule, most commonly the HLA-A*02:01 allele. This complex is a critical component of the immune system's surveillance mechanism, acting as a specific 'red flag' that allows CD8+ T-cells to recognize and destroy cells expressing PSA. In healthy individuals, PSA is a serine protease primarily produced by the prostate gland, but its overexpression is a hallmark of prostate cancer. In the field of immuno-oncology, the PSA-pMHC complex is a primary target for therapeutic vaccines and T-cell receptor (TCR)-based therapies. Vaccines like PROSTVAC utilize viral vectors to deliver PSA to APCs, which then process and present the PSA-pMHC complex to prime the patient's immune system against cancer cells. Similarly, TCR-T cell therapies are engineered to express receptors that specifically bind to the PSA-pMHC complex with high affinity. By targeting this complex, these therapies aim to induce a robust and specific cytotoxic immune response against malignant prostate tissue while minimizing damage to non-prostatic organs.

Other names

PSA peptide-HLA complexPSA-HLA-A2 complexKLK3 peptide-MHC complexProstate-specific antigen-derived peptide-MHC complexPSA-pMHC complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to the activation of cytotoxic T-lymphocytes (CTLs) and subsequent lysis of PSA-expressing tumor cells.