Brachyury peptide-Major Histocompatibility Complex (Brachyury-MHC)

Brachyury, also known as T-box transcription factor T, is a critical driver of the epithelial-mesenchymal transition (EMT) and is essential for mesoderm development during embryogenesis. While its expression is minimal in healthy adult tissues, it is significantly upregulated in various cancers, including chordoma and metastatic carcinomas of the lung, breast, and colon (Palena et al., 2007). The Brachyury peptide-MHC complex is formed when intracellular Brachyury protein is processed and its resulting peptides are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, typically HLA-A2 (Heery et al., 2015). This complex acts as a specific tumor-associated antigen that can be recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes. Therapeutic strategies targeting this complex include recombinant viral vaccines, such as MVA-Brachyury-TRICOM, and adoptive cell therapies using TCR-engineered T-cells (Hamilton et al., 2017). These treatments aim to induce a robust immune response against mesenchymal-like tumor cells, thereby inhibiting tumor growth and preventing metastatic spread.

Other names

T-box transcription factor T peptide-MHCBrachyury-HLA complexT-peptide-MHCBrachyury-MHC class I complex

The mechanism of action involves the presentation of Brachyury-derived immunogenic peptides by MHC class I molecules on the surface of tumor cells, which are then recognized by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, leading to targeted cell lysis (Palena et al., 2007).