Mutated BRAF neoantigen–Human Leukocyte Antigen complex (BRAF-neoantigen-HLA complex)

The Mutated BRAF neoantigen–Human Leukocyte Antigen (HLA) complex is a molecular assembly found on the surface of cancer cells, consisting of a peptide fragment derived from a mutated BRAF protein bound to an HLA molecule. BRAF is a serine/threonine-protein kinase that plays a critical role in the MAPK/ERK signaling pathway, which regulates cell growth and proliferation (UniProt P15056). The V600E mutation is the most common oncogenic driver in BRAF, leading to constitutive kinase activity and malignant transformation in diseases such as melanoma and colorectal cancer (PubMed: 25303982). When the mutated BRAF protein is processed by the cellular proteasome, the resulting neoantigenic peptides are presented by HLA Class I or Class II molecules to the immune system. This complex is a highly attractive therapeutic target because the mutated sequence is unique to tumor cells, allowing for high specificity in immunotherapies like TCR-engineered T-cells and neoantigen vaccines (PubMed: 30104341). By targeting this complex, the immune system can be precisely directed to eliminate cancer cells while sparing healthy tissues that express only the wild-type BRAF protein.

Other names

BRAF V600E neoantigen-HLA complexBRAF V600E-MHC complexMutated BRAF peptide-MHC complexBRAF V600E-HLA-A*02:01 complexBRAF V600E-HLA-DRB1*04:01 complex

Recognition of the specific mutated BRAF peptide presented by HLA molecules by T-cell receptors (TCRs), leading to the activation of cytotoxic T-lymphocytes and subsequent lysis of the tumor cell.