Mutant Ras peptide–MHC class I complex

The mutant Ras peptide–MHC class I complex is a heterotrimeric cell surface structure formed when peptides derived from RAS oncogenes carrying tumor-specific point mutations (such as KRAS G12C, G12V or Q61H/L/R) are processed and presented by major histocompatibility complex (MHC) class I molecules, typically in the context of a specific human leukocyte antigen (HLA) allele (e.g., HLA-A*01, HLA-A*03)[1][5][2]. These peptide–MHC complexes function as "neoantigens," marking tumor cells for recognition by cytotoxic CD8+ T cells[3][6]. Because RAS proteins are intracellular and not directly accessible to antibody or T cell therapies, the cell surface display of mutant RAS–derived peptides via MHC class I enables the development of targeted immunotherapies, including T cell–engaging bispecific antibodies and engineered T cell therapies[5][2]. The formation, abundance, and stability of these complexes are influenced by both the specific mutation, the surrounding peptide sequence, the MHC allele, and the dynamics of peptide loading and presentation[1]. Targeting these complexes is an area of active research for treatment of RAS-mutant cancers, with unique considerations for specificity, efficacy, and safety.

Other names

Mutant RAS peptide–MHC-I complexMutant KRAS/NRAS/HRAS peptide–HLA complexMutant RAS neoepitope–MHC complexMutant RAS peptide–HLA complex

Immune cell redirection (T cell activation and cytolytic activity via engagement of mutant RAS peptide–MHC by bispecific antibodies)[5]; Neoantigen-based recognition leading to targeted killing of cancer cells by engineered immune effectors[2][5]