[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

Perforin-2 is a pore-forming effector of endocytic escape in cross-presenting dendritic cells

Science. 2023 Jun 23;380(6651):1258-1265. doi: 10.1126/science.adg8802. Epub 2023 Jun 22.

Abstract

During initiation of antiviral and antitumor T cell-mediated immune responses, dendritic cells (DCs) cross-present exogenous antigens on major histocompatibility complex (MHC) class I molecules. Cross-presentation relies on the unusual "leakiness" of endocytic compartments in DCs, whereby internalized proteins escape into the cytosol for proteasome-mediated generation of MHC I-binding peptides. Given that type 1 conventional DCs excel at cross-presentation, we searched for cell type-specific effectors of endocytic escape. We devised an assay suitable for genetic screening and identified a pore-forming protein, perforin-2 (Mpeg1), as a dedicated effector exclusive to cross-presenting cells. Perforin-2 was recruited to antigen-containing compartments, where it underwent maturation, releasing its pore-forming domain. Mpeg1-/- mice failed to efficiently prime CD8+ T cells to cell-associated antigens, revealing an important role for perforin-2 in cytosolic entry of antigens during cross-presentation.

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • Cross-Priming / genetics
  • Cross-Priming / immunology
  • Dendritic Cells / immunology
  • Endocytosis* / genetics
  • Endocytosis* / immunology
  • Genetic Testing
  • Histocompatibility Antigens Class I
  • Mice
  • Pore Forming Cytotoxic Proteins* / genetics
  • Pore Forming Cytotoxic Proteins* / metabolism
  • Proteolysis

Substances

  • Antigens
  • Histocompatibility Antigens Class I
  • Mpeg1 protein, mouse
  • Pore Forming Cytotoxic Proteins