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The CD4+ T cell receptor recognizing IDH1 R132H–MHC II complexes is a specialized immune receptor that targets a specific neoantigen found in many low-grade and secondary high-grade gliomas (Platten et al., Nature, 2014). The IDH1 R132H mutation creates a unique peptide sequence that is not present in healthy tissue, making it an ideal target for immunotherapy (Schumacher et al., Nature Communications, 2014). When this mutant peptide is processed and presented by MHC class II molecules, specifically HLA-DRB1*01:01, it is recognized by these specific T-cell receptors. This recognition triggers a robust Th1-polarized immune response, characterized by the production of interferon-gamma and the recruitment of other immune effectors to the tumor site (Bunse et al., Nature Medicine, 2018). Therapeutic strategies leveraging this target include peptide vaccines, such as those tested in the NOA-16 clinical trial, and adoptive cell therapies using T cells engineered to express this specific receptor (Platten et al., Nature, 2021). Because the target is a neoantigen, these therapies typically exhibit high specificity for tumor cells with minimal off-target toxicity to normal brain tissue.
Recognition of the IDH1 R132H neoepitope presented by MHC class II molecules, leading to CD4+ T-cell activation and anti-tumor immune responses.
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