Patient-specific neoantigen peptide–HLA class I complex (NeoAg-HLA-I)

The patient-specific neoantigen peptide–HLA class I complex is a molecular assembly presented on the surface of tumor cells, consisting of a mutation-derived peptide bound to a specific HLA class I molecule (Schumacher & Schreiber, 2015). These neoantigens result from somatic mutations, such as non-synonymous single nucleotide variants (SNVs) or frameshifts, which are absent from the normal human proteome (Blass & Ott, 2021). Because they are not subject to central thymic tolerance, these complexes are highly immunogenic and can be recognized by the host's CD8+ T cells as 'non-self' (Yarchoan et al., 2017). The interaction between the T-cell receptor (TCR) and the neoantigen-HLA complex is the fundamental trigger for the adaptive immune system to selectively destroy cancer cells while sparing healthy tissue. Therapeutic interventions targeting these complexes include personalized neoantigen vaccines, such as mRNA-4157, and adoptive cell therapies using TCR-engineered T cells (Sahin & Türeci, 2018). Identifying these targets requires high-throughput sequencing of the tumor exome and sophisticated bioinformatic algorithms to predict peptide binding affinity to the patient's specific HLA alleles (Ott et al., 2017). Despite their potential, challenges remain regarding the heterogeneity of neoantigen expression and the potential for tumor escape through HLA loss or downregulation (Gubin et al., 2014). This target represents a cornerstone of precision oncology, shifting the focus from shared tumor antigens to truly individualized therapeutic strategies.

Other names

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

Recognition by cognate T-cell receptors (TCRs) leading to cytotoxic T lymphocyte (CTL) activation and tumor cell lysis.