KRAS mutant peptide–HLA class I complex (null)

The KRAS mutant peptide–HLA class I complex is a molecular structure on the surface of tumor cells that have acquired point mutations in the KRAS oncogene, most commonly at codon 12 (e.g., G12C, G12V, G12D). These mutations lead to the production of abnormal short peptides that, after intracellular processing, can bind to specific HLA class I alleles (such as HLA-A*11:01) and be displayed on the cell surface. These neoantigen complexes are recognized by cytotoxic CD8+ T cells via their T cell receptors (TCRs), enabling immune-mediated elimination of the tumor cells. The presentation of KRAS mutant peptides on HLA class I molecules thus represents a promising tumor-specific therapeutic target for immunotherapy approaches, including TCR-engineered T cells and cancer vaccines, as it combines the specificity of a cancer driver mutation with immune recognition machinery. Progress in this field includes development and validation of TCRs targeting specific KRAS mutant/HLA combinations, demonstrating successful tumor cell killing in preclinical models and early clinical studies. However, challenges remain, such as HLA allele diversity and tumor immune evasion through loss of antigen presentation.

Other names

Mutant KRAS peptide presented by MHC class IKRAS neoantigen–HLA class I complexmKRAS peptide–HLA-IKRAS G12C/G12D/G12V peptide–HLA class I complex (variant-specific)

Recognition of tumor neoantigen by T cells via TCR binding to the KRAS mutant peptide–HLA class I complex, resulting in activation of cytotoxic T lymphocytes and selective destruction of tumor cells expressing the mutation