Neoantigen-specific T-cell receptor-peptide-major histocompatibility complex (TCR-pMHC-neoantigen)

The neoantigen-specific T-cell receptor-peptide-major histocompatibility complex (TCR-pMHC) is the fundamental unit of immune recognition in oncology, though the target as phrased in the prompt is technically imprecise because MHC Class I molecules typically interact with CD8+ T cells, while MHC Class II molecules interact with CD4+ T cells (Schumacher & Schreiber, 2015; Blass & Ott, 2021). This complex forms when a TCR recognizes a tumor-specific mutated peptide (neoantigen) presented within the groove of an MHC molecule (Sahin & Türeci, 2018). Because neoantigens are derived from somatic mutations and are absent from healthy tissue, they bypass central thymic tolerance, allowing for high-affinity T-cell responses with minimal risk of autoimmunity (Schumacher & Schreiber, 2015; Ott et al., 2017). Therapeutic strategies targeting this axis include personalized neoantigen vaccines, such as mRNA-4157 and Autogene cevumeran, and TCR-engineered T-cell (TCR-T) therapies (Blass & Ott, 2021; Hu et al., 2021). These interventions aim to induce a potent and selective anti-tumor immune response by specifically engaging neoantigen-reactive T cells (Sahin & Türeci, 2018). However, clinical efficacy can be limited by tumor-mediated HLA downregulation, which prevents antigen presentation, or by the development of T-cell exhaustion within the immunosuppressive tumor microenvironment (Schumacher & Schreiber, 2015; Garrido et al., 2016).

Other names

Neoantigen-TCR-pMHC complexpMHC-TCR interactionTumor-specific antigen-MHC complexNeoepitope-MHC-TCR axis

Recognition of tumor-specific mutated peptides (neoantigens) presented on MHC molecules by T-cell receptors, triggering T-cell mediated cytotoxicity (CD8+) or helper (CD4+) immune responses.