RalBP1-associated Eps domain-containing protein 1 (Reps1) neoantigen peptide–MHC class I complex (Reps1-MHC-I)

The Reps1 neoantigen peptide–MHC class I complex is a tumor-specific molecular target consisting of a mutated peptide fragment derived from the RalBP1-associated Eps domain-containing protein 1 (Reps1) bound to a Major Histocompatibility Complex (MHC) class I molecule. This complex is primarily characterized in the context of the MC38 murine colon adenocarcinoma model, where a specific somatic mutation (P45A) creates a novel epitope that is not present in normal tissues (Yadav et al., Nature, 2014; Gubin et al., Nature, 2014). Because this neoantigen is uniquely expressed by tumor cells, it serves as a highly specific target for the immune system, particularly for CD8+ cytotoxic T cells (Gubin et al., Nature, 2014). Therapeutic strategies targeting this complex include personalized neoantigen vaccines and T-cell receptor (TCR) engineered T-cell therapies, which aim to induce or enhance a robust anti-tumor immune response (Yadav et al., Nature, 2014; Castle et al., Cancer Res, 2012). The biological significance of this complex lies in its ability to bypass central tolerance, as the mutated peptide is recognized as "non-self," thereby reducing the risk of autoimmune toxicity compared to traditional tumor-associated antigens (Gubin et al., Nature, 2014). However, clinical challenges include the potential for tumor immune escape through the downregulation of MHC molecules or the loss of the specific neoantigen (Yadav et al., Nature, 2014).

Other names

Reps1 P45A neoantigenMutant Reps1-H-2Db complexRalBP1-associated Eps domain-containing protein 1 neoepitopeMC38 neoantigen Reps1Reps1-MHC complex

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, triggering the release of perforins and granzymes to induce tumor cell apoptosis.