Perforin-2 is a Pore-forming Effector of Endocytic Escape in Cross-presenting Dendritic Cells

Overview

Journal Science

Specialty Science

Date 2023 Jun 22

PMID 37347855

Authors

Pablo Rodriguez-Silvestre

Marco Laub

Patrycja A Krawczyk

Alexandra K Davies

Julia P Schessner

Reejuana Parveen

Benjamin J Tuck

William A McEwan

Georg H H Borner

Patrycja Kozik

Affiliations

Soon will be listed here.

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 (), 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. 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.

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