KRAS wild-type peptide–HLA-A*11:01 complex (KRAS WT-HLA-A*11:01)

The KRAS wild-type peptide–HLA-A*11:01 complex is a molecular assembly consisting of a non-mutated 10-amino acid peptide (typically VVVGAGAGVG) derived from the KRAS protein, presented by the Human Leukocyte Antigen (HLA) allele A*11:01 (Wang et al., 2021). This complex is expressed on the surface of normal cells in individuals who carry the HLA-A*11:01 allele, which is particularly prevalent in East Asian populations (Gonzalez-Galarza et al., 2020). In the field of oncology, this complex is not a target for destruction but rather a critical safety benchmark for therapies targeting KRAS mutations, such as G12D or G12V. Because the mutant peptides often differ from the wild-type by only a single amino acid, engineered T-cell receptors (TCRs) must be meticulously designed to distinguish between the two to avoid off-target toxicity (Bear et al., 2022). If a therapeutic TCR cross-reacts with this wild-type complex, it could lead to the destruction of healthy tissues and severe clinical adverse events. Consequently, the KRAS wild-type peptide–HLA-A*11:01 complex is used extensively in preclinical screening to ensure the high specificity of TCR-T cell therapies and neoantigen vaccines (Sim et al., 2020). Understanding its structural and binding characteristics is essential for developing safe and effective precision immunotherapies for KRAS-driven cancers.

Other names

KRAS WT-HLA-A11HLA-A*11:01-KRAS(7-16) WTWild-type KRAS peptide-MHC complexHLA-A*11:01-restricted KRAS wild-type antigen

The complex serves as a ligand for T-cell receptors (TCRs). In immunotherapy development, it acts as a negative selection target; drugs like TCR-T cells are engineered to avoid binding this wild-type complex while maintaining high affinity for mutant KRAS-HLA complexes to ensure tumor-specific activity and avoid healthy tissue destruction (Sim et al., 2020).