Mutant BRAF neoantigen HLA–peptide complex (Mutant BRAF-HLA complex)

Mutant BRAF neoantigen HLA–peptide complexes are tumor-specific targets formed when mutated BRAF proteins, primarily the V600E variant, are intracellularly processed into short peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (Cancer Res 2006; 66(6): 3287-93). These complexes represent a "non-self" signal that can be recognized by the adaptive immune system, specifically by CD8+ T cells, making them highly attractive for precision immunotherapies such as T-cell receptor (TCR)-engineered T-cell therapy and neoantigen vaccines (JITC 2023; 11:e007097). The BRAF V600E mutation is a critical driver in several cancers, including melanoma, colorectal cancer, and papillary thyroid carcinoma, where it leads to constitutive activation of the MAPK signaling pathway. Therapeutic strategies aim to exploit the unique structural features of the mutant peptide-HLA (pHLA) complex to selectively eliminate malignant cells while sparing normal cells expressing wild-type BRAF. However, the clinical utility of these targets depends on the patient's HLA genotype and the efficiency of the tumor's antigen presentation machinery. Challenges such as HLA downregulation and low levels of naturally presented neoepitopes can hinder the effectiveness of these treatments (Front. Immunol. 2021; 12:734530).

Other names

BRAF V600E neoantigen-HLA complexBRAF V600E-MHC complexBRAF V600E-HLA-A*02:01 complexBRAF V600E-HLA-A*03:01 complexBRAF V600E-HLA-A*11:01 complexMutant BRAF peptide-HLA complex

T-cell receptor (TCR) binding to the specific mutant peptide-HLA complex on the tumor cell surface, triggering T-cell activation and subsequent cytotoxic lysis of the target cell.