Histone H3 lysine 27-to-methionine (H3K27M) neoepitope presented by HLA class II (H3K27M-HLA-II)

The H3K27M neoepitope presented by HLA class II is a tumor-specific antigen arising from a recurrent somatic mutation in histone H3 genes, most commonly H3F3A, where lysine 27 is replaced by methionine. This mutation is a defining molecular feature of diffuse midline gliomas (DMG), including diffuse intrinsic pontine glioma (DIPG), and leads to global loss of H3K27 trimethylation and oncogenic epigenetic reprogramming (Chheda et al., Nature, 2018). When the mutated peptide sequence is processed and presented by Human Leukocyte Antigen (HLA) class II molecules, specifically HLA-DR, it can be recognized by the immune system as a foreign neoantigen. Therapeutic targeting of this complex primarily involves peptide vaccines and T-cell receptor (TCR) therapies designed to elicit a CD4+ T-cell response (Mueller et al., JCO, 2020). Because the H3K27M mutation is highly specific to the tumor and absent in normal tissues, it serves as a high-priority target for precision immunotherapy in aggressive pediatric brain cancers. Clinical success depends on the patient's HLA profile, as specific alleles like HLA-DRB1*01:01 are required to effectively present the neoepitope to T cells (Ochs et al., OncoImmunology, 2017).

Other names

H3.3K27M neoantigenH3K27M-MHC-II complexH3K27M-HLA-DR complexHistone H3.3 K27M mutation-derived neoepitope

Induction of antigen-specific CD4+ T-cell mediated immune response through the recognition of the mutated histone H3 peptide sequence presented by HLA class II molecules on the surface of tumor cells or antigen-presenting cells.