Tumor neoantigen-HLA class I complex (NeoAg-HLA-I)

Tumor neoantigen-HLA class I complexes are unique molecular targets formed when mutated proteins within a cancer cell are degraded into peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules (Schumacher & Schreiber, 2015, Science). These neoantigens arise from somatic mutations, such as single nucleotide variants or frameshifts, and are absent from the normal human proteome, providing high tumor specificity (Blass & Ott, 2021, Nature Reviews Clinical Oncology). The recognition of these complexes by CD8+ T-cell receptors is a critical step in the endogenous anti-tumor immune response. Therapeutic interventions, including personalized mRNA vaccines and TCR-engineered T-cell therapies, aim to enhance or direct the immune system to specifically attack cells displaying these neoepitopes (Ott et al., 2017, Nature). However, challenges remain regarding the heterogeneity of neoantigen expression and the potential for tumors to evade detection by downregulating HLA expression or through the loss of HLA heterozygosity (McGranahan et al., 2017, Cell).

Other names

Neoepitope-HLA complexTumor-specific antigen (TSA)Neoantigen-MHC class I complexpHLA-I complexPersonalized neoantigen

Recognition of the peptide-HLA complex by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, triggering the release of perforins and granzymes to induce apoptosis in the target tumor cell.