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

The HLA-A*11:01–KRAS wild-type peptide complex is a molecular assembly consisting of the Class I Human Leukocyte Antigen (HLA) allele A*11:01 and a peptide fragment derived from the non-mutated (wild-type) KRAS protein. The peptide typically presented is the 10-mer sequence VVVGAVGVGK, spanning residues 7 through 16 of the KRAS protein (Wang et al., 2016). This complex is expressed on the surface of nearly all nucleated cells, as KRAS is a ubiquitous GTPase involved in essential cellular signaling pathways (Simanshu et al., 2017). In the context of drug discovery, this complex is not a therapeutic target but rather a critical safety counter-target used to evaluate the specificity of T-cell receptor (TCR)-based therapies and vaccines (Ke et al., 2023). Because KRAS mutations (like G12D or G12V) are highly prevalent in pancreatic, colorectal, and lung cancers, researchers develop immunotherapies to target the mutant peptide-HLA complex. A primary challenge is ensuring these therapies do not cross-react with the wild-type complex, which would lead to "on-target, off-tumor" toxicity and widespread destruction of healthy tissue (June et al., 2018). Therefore, the HLA-A*11:01–KRAS wild-type complex serves as a negative control in the development of precision immunotherapies for KRAS-driven malignancies.

Other names

HLA-A*11:01-KRAS(7-16) WTMHC-I KRAS wild-type complexHLA-A11:01-KRAS WTHLA-A*11:01-VVVGAVGVGK complex

Not applicable as a therapeutic target; serves as a safety benchmark for specificity in immunotherapy development.