Neoantigen–Human Leukocyte Antigen class I complex (Neoantigen–HLA-I complex)

Neoantigen–Human Leukocyte Antigen (HLA) class I complexes are molecular assemblies found on the surface of tumor cells, consisting of a mutated peptide (neoantigen) derived from somatic mutations and an HLA class I molecule (PMID: 28410993). These complexes are essential for the immune system's ability to recognize cancer cells as non-self, as the neoantigens are not present in healthy tissues. When a T-cell receptor (TCR) on a CD8+ cytotoxic T lymphocyte binds to a specific neoantigen–HLA complex, it triggers the release of perforins and granzymes, leading to the targeted destruction of the tumor cell (PMID: 30726505). Because neoantigens are highly specific to individual tumors, they are ideal targets for personalized immunotherapies, such as neoantigen-based vaccines and TCR-engineered T-cell (TCR-T) therapies. Despite their potential, the effectiveness of targeting these complexes can be limited by tumor-driven HLA downregulation, which allows cancer cells to evade immune detection (PMID: 29739771). Additionally, the high degree of polymorphism in HLA genes and the unique nature of neoantigens in each patient necessitate highly personalized diagnostic and therapeutic approaches.

Other names

Neoepitope–MHC class I complexTumor-specific antigen–HLA complexMutant peptide–HLA-I complexpHLA-I complexNeoantigen–MHC-I complex

Recognition of the peptide-HLA complex by specific T-cell receptors (TCRs) on CD8+ T cells, inducing cytotoxic activity and tumor cell apoptosis (PMID: 31570881).