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The **Histone H3.3 K27M peptide presented on HLA-A*02:01** is a neoantigen complex consisting of a mutant peptide derived from the H3.3 histone variant (with a lysine-to-methionine substitution at position 27), bound by the human leukocyte antigen HLA-A*02:01. This neoantigen is frequently found in diffuse midline glioma (DMG), including pediatric diffuse intrinsic pontine glioma (DIPG), and has been the focus of cancer immunotherapy research, including peptide vaccines and chimeric antigen receptor (CAR) T cell strategies[1][4][5]. While preclinical studies demonstrated binding of the mutant peptide to HLA-A*02:01 and in vitro immune recognition, recent research has shown that the natural presentation level of this peptide-MHC complex on tumor cells is extremely low or undetectable, which limits its practicality as a therapeutic immunotherapy target[2][3]. Nevertheless, it remains under clinical investigation as a model for targeting tumor-specific, mutation-driven neoantigens in cancer.
Induction of CD8⁺ T cell immunity via peptide vaccine targeting the presented neoantigen[4][5]\nRe-direction of cytotoxic T lymphocytes (CTLs) or CAR-T cells to target tumor cells presenting the H3.3K27M peptide-HLA complex[2][3]
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