KRAS G12D peptide–MHC class I complex

The KRAS G12D peptide–MHC class I complex is a cell-surface molecular target resulting from the presentation of a short peptide (containing the oncogenic G12D substitution: glycine to aspartic acid at position 12) from the KRAS protein, bound within the peptide-binding groove of a human MHC class I molecule (notably HLA-A*11:01 or HLA-C*08:02). This neoantigenic complex is uniquely presented by tumor cells carrying the KRAS G12D mutation and is recognized by specific T cell receptors, enabling development of personalized immunotherapies such as adoptive T cell therapies or engineered TCR therapeutics. The biological and therapeutic relevance of this complex arises from its tumor-specificity—the G12D peptide is generated only in mutant cells and, when presented by defined MHC class I alleles, can be specifically targeted by T cells without affecting normal tissues. Structural studies have elucidated how the mutant peptide interacts with the MHC and how specificity for the G12D residue enables immune discrimination. This pMHC complex is currently a major focus in precision oncology for HLA-matched, KRAS G12D–mutated cancers.

Other names

KRAS G12D neoantigen–MHC complexKRAS G12D mutant peptide–MHC class I complexKRAS G12D (pMHC)KRAS G12D peptide–HLA complexKRAS G12D–HLA-A*11:01 complexKRAS G12D–HLA-C*08:02 complex

Targeted TCR binding: Engineered T cell receptors bind to KRAS G12D peptide presented on MHC class I, triggering T cell–mediated killing of tumor cells expressing the neoantigen. Adoptive T cell therapy: Transfer of T cells carrying high-affinity TCRs specific for the KRAS G12D–MHC complex, enabling recognition and destruction of cancer cells bearing the mutation.