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

The HLA-DRB1*15:01–KRAS G12V-derived peptide complex is a major histocompatibility complex (MHC) class II assembly that presents a mutated fragment of the KRAS protein to the immune system (Tran et al., 2016, Science). KRAS is a small GTPase that acts as a molecular switch for cell growth, and the G12V mutation is a common oncogenic driver found in pancreatic, colorectal, and lung cancers (Prior et al., 2020, Cancer Research). This specific complex is formed when the HLA-DRB1*15:01 allele binds and displays the G12V neoantigen on the cell surface, making it a target for CD4+ T-cell recognition (Sim et al., 2020, Journal for ImmunoTherapy of Cancer). Its primary biological role is to facilitate the recognition of tumor-specific mutations by the adaptive immune system, potentially leading to tumor cell destruction. In the context of oncology, this complex serves as a highly specific therapeutic target for TCR-engineered T-cell (TCR-T) therapies and neoantigen vaccines (Bear et al., 2020, Journal of Clinical Investigation). By targeting this complex, clinicians aim to direct the immune system to selectively eliminate KRAS G12V-positive tumor cells while sparing healthy tissues that lack the mutation. Because the G12V mutation is absent in healthy tissue, this complex represents a high-value target for precision immunotherapy with a potentially wide therapeutic window.

Other names

HLA-DRB1*15:01–KRAS G12V neoantigen complexMHC Class II–KRAS G12V complexKRAS G12V:HLA-DRB1*15:01

T-cell receptor (TCR) binding to the peptide-MHC complex, triggering CD4+ T-cell activation and anti-tumor effector functions.