Neoantigen-Human Leukocyte Antigen Class I complex (NeoAg-HLA-I)

Neoantigens are unique, non-self peptides derived from tumor-specific somatic mutations that are not found in the normal human genome. These peptides are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) Class I molecules, forming a complex that can be recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells (Schumacher & Schreiber, 2015, Science). Because these complexes are absent from healthy tissues, they represent highly specific targets for immunotherapy, which helps to minimize the risk of autoimmune-like toxicities (Sahin & Türeci, 2018, Science). Therapeutic approaches targeting these complexes include personalized cancer vaccines, which prime the immune system to recognize specific neoepitopes, and adoptive cell therapies using TCR-engineered T cells (Gubin et al., 2015, Nature). Despite their potential, the effectiveness of targeting neoantigen-HLA complexes is often challenged by tumor heterogeneity and the ability of cancer cells to escape immune detection by downregulating HLA expression or other components of the antigen presentation pathway (Hacohen et al., 2013, Cancer Immunology Research).

Other names

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

Recognition of the specific neoepitope-HLA complex by T-cell receptors (TCRs) leads to the activation of cytotoxic T lymphocytes and subsequent lysis of the tumor cell.