Patient-specific neoepitope–Major Histocompatibility Complex class I complex (Neoepitope-MHC-I complex)

A patient-specific neoepitope–Major Histocompatibility Complex (MHC) class I complex is a molecular assembly presented on the surface of malignant cells, consisting of a tumor-specific mutated peptide (neoepitope) bound to a patient's own MHC class I molecule (Nature Reviews Cancer, 2021). These neoepitopes result from somatic mutations, such as non-synonymous single nucleotide variants (SNVs) or indels, and are not found in the normal genome, providing a high degree of tumor specificity (Science, 2019). The primary biological role of this complex is to serve as a ligand for the T-cell receptor (TCR) on CD8+ cytotoxic T lymphocytes, thereby triggering an adaptive immune response against the tumor (Nature, 2017). In therapeutic contexts, these complexes are targeted by personalized cancer vaccines, such as mRNA-4157 and BNT122, which aim to prime and expand the patient's endogenous T-cell population to recognize these unique markers (Cell, 2020). Additionally, adoptive cell therapies utilize TCR-engineered T cells specifically designed to bind these patient-specific complexes. While highly promising for precision oncology, challenges include the requirement for intensive bioinformatic prediction of peptide-MHC binding and the risk of tumor escape through the loss of HLA expression or antigen processing machinery (Journal of Clinical Investigation, 2019).

Other names

Neoantigen-MHC complexTumor-specific antigen-MHC complexpHLA-I complexMutant peptide-HLA complexPersonalized neoantigen-HLA complex

Binding to T-cell receptors (TCRs) on CD8+ T cells to initiate cytotoxic immune responses against tumor cells presenting the specific mutated peptide.