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Cannabinoids act as H3k27ac Epigenetic Modifiers of Genes Regulating MHC-I Antigen Processing and Presentation that Induce Cytolytic T Lymphocyte Recognition of Metastatic Cancers

ABSTRACT: Cannabinoids act as H3k27ac Epigenetic Modifiers of Genes Regulating MHC-I Antigen Processing and Presentation that Induce Cytolytic T Lymphocyte Recognition of Metastatic Cancers

ORGANISM(S): Mus musculus

PROVIDER: GSE179897 | GEO | 2023/07/14

REPOSITORIES: GEO

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Cannabinoids act as H3k27ac Epigenetic Modifiers of Genes Regulating MHC-I Antigen Processing and Presentation that Induce Cytolytic T Lymphocyte Recognition of Metastatic Cancers

Project description:Cannabinoids act as H3k27ac Epigenetic Modifiers of Genes Regulating MHC-I Antigen Processing and Presentation that Induce Cytolytic T Lymphocyte Recognition of Metastatic Cancers

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Global gene expression profile of Japanese encephalitis virus(JEV) infected cytolytic B16F10 and Non-cytolytic JEV resistant B16F10r

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Direct recognition by alphabeta cytolytic T cells of Hfe, a MHC class Ib molecule without antigen-presenting function.

Project description:Crystallographic analysis of human Hfe has documented an overall structure similar to classical (class Ia) MHC molecules with a peptide binding groove deprived of ligand. Thus, to address the question of whether alphabeta T cells could recognize MHC molecules independently of bound ligands, we studied human and mouse Hfe interactions with T lymphocytes. We provide formal evidence of direct cytolytic recognition of human Hfe by mouse alphabeta T cell receptors (TCR) in HLA-A*0201 transgenic mice and that this interaction results in ZAP-70 phosphorylation. Furthermore, direct recognition of mouse Hfe molecules by cytotoxic T lymphocytes (CTLs) was demonstrated in DBA/2 Hfe knockout mice. These CTLs express predominantly two T cell antigen receptor alpha variable gene segments (AV6.1 and AV6.6). Interestingly, in wild-type mice we identified a subset of CD8+ T cells positively selected by Hfe that expresses the AV6.1/AV6.6 gene segments. T cell antigen receptor recognition of MHC molecules independently of bound ligand has potential general implications in alloreactivity and identifies in the Hfe case a cognitive link supporting the concept that the immune system could be involved in the control of iron metabolism.

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Project description:Natural antibodies (NAb) and complement (C') are important regulators of immune system activation. We have shown previously that the galactosyl-alpha1,3-galactosyl (Gal alpha1,3Gal) xenoantigen and the similar ABO histo-blood group antigens are transferred onto virus from the producer cell, resulting in sensitisation of the virus to the respective NAb in a C'-dependent manner. Here we show that measles virus (Mv) that expresses Gal alpha1,3Gal termini can drive the proliferation of human T cells in the presence of serum and autologous DC, whereas without such targets, measles, as expected, suppress T cell reactivity. The use of affinity-purified NAb to Gal alpha1,3Gal and rabbit C' demonstrated the components in human serum responsible for this effect. Proteasome inhibition and blocking of antigen presentation showed that the increased T cell proliferation was mediated by MHC class I cross-presentation of immune complexes. These results lend further support to the idea that polymorphic carbohydrates of the Gal alpha1,3Gal/ABO type serve as important targets for NAb and C' and that their expression on virus has influenced their evolution by contributing to protection against viral transmission within as well as between species. The adjuvance effect of this recognition, acting as a bridge between the natural innate and adaptive immune systems, also has important implications for vaccine development.

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