KRAS G12V peptide bound to HLA-A*11:01 major histocompatibility complex (KRAS G12V-HLA-A*11:01 pMHC complex)

The KRAS G12V peptide/HLA-A*11:01 complex is a synthetic or naturally processed peptide from the oncogenic KRAS protein with a glycine-to-valine substitution at position 12 (G12V), bound in the peptide groove of HLA-A*11:01, a human MHC class I molecule. The complex is presented on the surface of tumor cells carrying the KRAS G12V mutation and the HLA-A*11:01 allele, enabling specific recognition by CD8+ T-cells or engineered TCRs. The structural basis for selective immune recognition relies on hydrophobic and hydrogen bond interactions within the binding groove, resulting in stable antigen presentation and immunogenicity, making it a prime target for adoptive cell therapy and immune-based cancer treatments[1][3][5][7]. The therapeutic targeting of this complex is limited to patients expressing the HLA-A*11:01 allele and the KRAS G12V mutant peptide; these requirements pose notable safety and stratification challenges. The KRAS G12V peptide is typically 9 amino acids long (e.g., VVGAVGVGK), specifically binding with high affinity and stability in the HLA-A*11:01 groove[1][3][7]. The crystal structure and binding interactions have been elucidated, confirming its suitability as a cancer immunotherapy target for TCR and TCRm approaches[1][3][7]. It is not a traditional receptor or enzyme but a peptide-MHC complex critical in antigen presentation and immune recognition[6][8].

Other names

KRAS-G12V/HLA-A*11:01 complexKRAS G12V neoantigen/HLA-A*11:01KRAS G12V-HLA-A*11:01 peptide–MHC

Recognition of mutant KRAS peptide presented on HLA-A*11:01 by engineered TCRs or TCRm antibodies leads to targeted killing of tumor cells. Activation of CD8+ cytotoxic T-lymphocytes by pMHC complex triggers apoptosis of target cells.