Mutated epidermal growth factor receptor peptide–major histocompatibility complex class I complex (null)

The mutated EGFR peptide–MHC complex is a molecular entity formed when an MHC class I molecule (encoded by HLA genes) displays a peptide from a mutated form of the epidermal growth factor receptor protein on the surface of a cell[6][3][1][2]. Such mutated EGFR-derived peptides, known as neoantigens, are formed by proteasomal fragmentation of intracellular EGFR proteins carrying mutations (commonly seen in cancers like NSCLC)[3][6]. These neoantigen peptides are loaded onto MHC I molecules in the endoplasmic reticulum, processed by peptide editors, and eventually presented on the cell surface. They can then be recognized by cytotoxic CD8+ T cells whose T cell receptors (TCRs) are specific for the mutant peptide–MHC complex. This recognition triggers targeted immune responses against tumor cells harboring EGFR mutations. The effectiveness of this system depends on the peptide’s affinity for the specific HLA allele and the immunogenicity of the mutant peptide relative to the wild-type peptide. Such complexes are foundational to several forms of cancer immunotherapy and T cell–based diagnostics. The downregulation of MHC I presentation or similarity between mutant and wild-type peptides may limit therapeutic efficacy or pose safety risks[3][6][5][2][7].

Other names

EGFR mutant peptide–MHC complexEGFR neoantigen–MHC complexEGFR pMHC complexMutant EGFR–HLA complex

TCR activation: Recognition of mutant EGFR peptide–MHC complexes by cytotoxic T lymphocytes leads to targeted killing of tumor cells carrying mutated EGFR. Cancer immunotherapy: Adoptive T cell transfer or engineered TCR therapies specifically target cells presenting neoantigens derived from mutated EGFR.