| First Author | Rodríguez-Silvestre P | Year | 2023 |
| Journal | Science | Volume | 380 |
| Issue | 6651 | Pages | 1258-1265 |
| PubMed ID | 37347855 | Mgi Jnum | J:337206 |
| Mgi Id | MGI:7493537 | Doi | 10.1126/science.adg8802 |
| Citation | Rodriguez-Silvestre P, et al. (2023) Perforin-2 is a pore-forming effector of endocytic escape in cross-presenting dendritic cells. Science 380(6651):1258-1265 |
| abstractText | 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. |
