MHC class II–restricted CD4+ T cell receptor specific for the H3K27M neoantigen (H3K27M-specific MHC-II TCR)

MHC class II–restricted CD4+ T cell receptors (TCRs) specific for the H3K27M neoantigen are specialized immune receptors that recognize a specific mutation in histone H3 (lysine 27 to methionine) [1, 2]. This mutation is a hallmark of diffuse midline gliomas (DMG), including diffuse intrinsic pontine glioma (DIPG), which are aggressive and often fatal pediatric brain tumors [1, 3]. These TCRs are restricted by MHC class II molecules, such as HLA-DR and HLA-DQ, and are primarily expressed on CD4+ T cells [1, 2]. Upon recognition of the H3K27M peptide-MHC complex, these receptors trigger T-cell activation, leading to the secretion of pro-inflammatory cytokines like interferon-gamma (IFN-γ) and the orchestration of a comprehensive antitumor immune response [1, 2]. Therapeutic strategies leveraging these TCRs include the development of adoptive TCR-engineered T-cell therapies and the use of long peptide vaccines designed to expand these specific T-cell populations in patients [2, 4]. Clinical evidence suggests that these MHC class II-restricted responses are vital for optimal antitumor immunity and can contribute to significant clinical outcomes, including complete remission in some cases [1, 2].

Other names

H3.3K27M-specific T-cell receptorH3K27M-reactive T-cell receptorMHC-II restricted H3K27M TCRCD4+ H3K27M-specific TCRHistone H3K27M-specific T-cell receptor

Peptide vaccines target these receptors by inducing their expansion and activation through the presentation of the H3K27M neoantigen on MHC class II molecules by antigen-presenting cells [1, 2]. Adoptive TCR-T cell therapies utilize these receptors to engineer T cells that can directly recognize and respond to H3K27M-mutant tumor cells, triggering a targeted immune attack [2, 3].