KRAS G12V peptide–major histocompatibility complex class I complex (KRAS G12V pMHC-I complex)

The **KRAS G12V peptide–MHC class I complex** is a molecular structure in which a 9- or 10-amino acid peptide derived from the **KRAS protein containing the oncogenic glycine-to-valine substitution at position 12 (G12V)** is bound and presented on the cell surface by a **major histocompatibility complex class I (MHC-I)** molecule—most frequently, human HLA-A*11:01 or HLA-A*03:01[1][2][4][7]. This neoantigen–MHC complex serves as a highly specific immunotherapeutic target for T cell receptor (TCR)–engineered T cells and antibody-like molecules, because the G12V mutation is a driver mutation commonly found in cancers and absent from normal tissues. The structural basis of TCR (or TCR-mimetic) recognition is well characterized: the mutant valine at position 12 creates altered peptide conformation and hydrophobicity, which enable discrimination by immune effectors engineered to target this complex[1][2][4][7]. Targeting this complex allows for selective immune recognition and destruction of tumor cells harboring the KRAS G12V mutation, provided the correct HLA type is present. No small-molecule drugs directly bind this complex, but several forms of immune therapies (e.g., TCR-T cells and CARs) are in development that specifically recognize or exploit this peptide–MHC structure as a therapeutic target[5][6]. Safety and efficacy depend heavily on the specificity for the mutant peptide, the patient’s HLA background, and avoiding off-target effects.

Other names

KRAS G12V neoantigen–MHC complexKRAS G12V–HLA complexKRAS G12V–pHLA complexKRAS mutant peptide–MHC complex

Immune cell targeting: TCR-engineered T cells or antibody-like molecules bind the KRAS G12V peptide–MHC complex, directing an immune response specifically against mutant tumor cells expressing this neoantigen[1][2][4][5]