Cyclooxygenase-2-derived peptide–Major Histocompatibility Complex (COX-2/MHC complex)

The Cyclooxygenase-2 (COX-2)-derived peptide–Major Histocompatibility Complex (MHC) is a tumor-associated antigen found on the surface of various cancer cells. COX-2, also known as Prostaglandin-endoperoxide synthase 2 (PTGS2), is an enzyme that is typically overexpressed in malignancies such as colorectal, breast, and lung cancers, where it contributes to tumor progression and immune evasion (Source: PubMed PMID: 15026324). Intracellular COX-2 proteins are processed by the proteasome into short peptides, which are then loaded onto MHC Class I molecules (most commonly HLA-A*02:01) and transported to the cell surface (Source: PubMed PMID: 11160599). This specific peptide-MHC complex acts as a flag for the immune system, allowing for the selective identification of malignant cells by cytotoxic T lymphocytes. Therapeutic strategies targeting this complex include peptide-based vaccines designed to prime the immune system and TCR-engineered T-cell (TCR-T) therapies that provide a direct mechanism for tumor cell lysis (Source: PubMed PMID: 18487465). Because COX-2 expression is significantly higher in tumor tissues compared to most healthy tissues, this complex represents a promising target for precision immunotherapy. However, careful monitoring for off-tumor effects is necessary, as COX-2 can be induced in normal tissues during inflammatory responses (Source: PubMed PMID: 21149614).

Other names

COX-2/HLA complexPTGS2 peptide-MHCHLA-A*02:01/COX-2(95-103)COX-2 peptide-HLA-A2 complex

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) triggers the activation of cytotoxic T lymphocytes (CTLs), leading to the release of perforins and granzymes and subsequent apoptosis of the target tumor cell.