HLA-DRB1*15:01–KRAS G12V peptide complex (HLA-DRB1*15:01–KRAS G12V)

The HLA-DRB1*15:01–KRAS G12V peptide complex is a specific molecular assembly consisting of a mutated KRAS peptide (G12V) bound to the Human Leukocyte Antigen (HLA) Class II molecule DRB1*15:01 (UniProt P01911, P01116). This complex serves as a neoantigen, a tumor-specific marker that can be recognized by the immune system, particularly CD4+ T cells, to distinguish malignant cells from healthy tissue (PubMed: 27959611). In many aggressive cancers, such as pancreatic ductal adenocarcinoma and colorectal cancer, the KRAS G12V mutation is a primary driver of oncogenesis, and its presentation on the cell surface via HLA molecules makes it a prime target for immunotherapy (PubMed: 32034047). Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cell therapies and neoantigen-based vaccines designed to induce a potent anti-tumor immune response. By specifically binding to this complex, TCR-T cells can selectively identify and destroy cells harboring the mutation while sparing those that do not. However, the clinical efficacy of such treatments is strictly dependent on the patient's HLA-DRB1*15:01 genotype and the stable expression of the complex on the tumor surface. Potential safety concerns include off-target effects if the TCR cross-reacts with wild-type KRAS or other similar peptide-MHC complexes.

Other names

HLA-DRB1*15:01-KRAS G12V neoantigen complexMHC Class II-KRAS G12V complexKRAS G12V/HLA-DRB1*15:01 complexHuman leukocyte antigen DRB1*15:01-KRAS G12V

T-cell receptor (TCR) recognition of the peptide-MHC complex triggers T-cell activation and subsequent lysis of tumor cells expressing the KRAS G12V mutation.