Cytochrome c oxidase subunit 1-derived peptide-MHC complex (COX1-pMHC)

Cytochrome c oxidase subunit 1 (COX1), also known as MT-CO1, is a key protein encoded by mitochondrial DNA that serves as the main catalytic subunit of the mitochondrial respiratory chain complex IV (UniProt P00395). Beyond its role in oxidative phosphorylation, COX1-derived peptides can be processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I and II molecules, acting as mitochondrial-derived antigens (MiDAs) (Pierini et al., 2022). In various malignancies, these peptides function as tumor-associated mitochondrial antigens (TAMAs) due to the metabolic reprogramming and frequent mitochondrial DNA mutations characteristic of cancer cells (PubMed: 26103414). These peptide-MHC complexes are emerging as promising targets for immunotherapy, particularly for T-cell receptor (TCR) engineered T-cell therapies and personalized cancer vaccines. By targeting these specific complexes, the immune system can be directed to recognize and eliminate tumor cells that exhibit aberrant mitochondrial protein presentation. However, a primary challenge in targeting COX1-pMHC is the ubiquitous nature of the parent protein, which necessitates precise selection of tumor-specific peptides to avoid off-target effects on healthy tissues.

Other names

MT-CO1-derived peptidesMitochondrial-derived antigensMiDAsTumor-associated mitochondrial antigensTAMAsCytochrome c oxidase subunit ICOX1-pMHC

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