Prostate-specific antigen-specific T-cell receptor–Major Histocompatibility Complex class I interaction (PSA-TCR–MHC I)

The Prostate-specific antigen-specific T-cell receptor–Major Histocompatibility Complex class I (PSA-TCR–MHC I) interaction is a fundamental component of the cellular immune response against prostate cancer (Heiser et al., 2000, PMID: 10411435). Prostate-specific antigen (PSA), or Kallikrein-3 (KLK3), is a serine protease primarily produced by the prostate gland and is a well-established biomarker for prostate malignancy. In the context of immunotherapy, PSA-derived peptides are presented on the surface of cancer cells by MHC Class I molecules, typically HLA-A*02:01. The specific recognition of these peptide-MHC complexes by T-cell receptors (TCRs) on CD8+ T cells is essential for the induction of a targeted cytotoxic response. This interaction triggers the release of perforin and granzymes, leading to the selective destruction of PSA-positive tumor cells. Therapeutic strategies such as TCR-engineered T-cell (TCR-T) therapy and PSA-based vaccines (e.g., PROSTVAC) aim to exploit or enhance this interaction to treat metastatic or castration-resistant prostate cancer (Madan et al., 2009, PMID: 19712002). However, challenges include the potential for on-target off-tumor effects on normal prostate tissue and the development of resistance through antigen loss or MHC downregulation (Gulley et al., 2019, PMID: 30635333).

Other names

PSA-TCR-MHC complexKLK3-specific TCR-HLA interactionPSA-peptide-HLA-A*02:01 complexPSA-specific TCR-MHC I synapse

T-cell receptor-mediated recognition of PSA-derived peptides presented by MHC Class I molecules, triggering cytotoxic T-lymphocyte activation and subsequent lysis of PSA-expressing cells.