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12:48
Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
Published on: August 21, 2017
IRAP identifies an endosomal compartment required for MHC class I cross-presentation
Loredana Saveanu1, Oliver Carroll, Mirjana Weimershaus
1INSERM, U580, 75015 Paris, France; Université Paris Descartes, Faculté de Médecine René Descartes, 75015 Paris, France.
Science (New York, N.Y.)
|June 6, 2009
Summary
Insulin-regulated aminopeptidase (IRAP) plays a key role in cross-presentation by trimming peptides in endosomes for Major histocompatibility complex (MHC) class I molecules. This finding clarifies cellular compartments involved in antigen presentation.
Area of Science:
- Immunology
- Cell Biology
- Proteostasis
Background:
- Major histocompatibility complex (MHC) class I molecules present peptides from cytosolic proteins to cytotoxic T lymphocytes.
- Cross-presentation allows dendritic cells to present exogenous antigens via MHC class I, but involved cellular compartments are not fully understood.
Purpose of the Study:
- To investigate the role of peptide trimming in the cellular mechanisms of cross-presentation.
- To identify specific cellular compartments and enzymes involved in the cross-presentation pathway.
Main Methods:
- Immunofluorescence microscopy to localize IRAP and MHC class I in human dendritic cells.
- CRISPR/Cas9 gene editing to create IRAP-deficient dendritic cells.
- In vitro and in vivo assays to assess cross-presentation efficiency.
Main Results:
- Insulin-regulated aminopeptidase (IRAP) was localized to a Rab14+ endosomal compartment, interacting with MHC class I molecules.
- IRAP deficiency impaired cross-presentation in both in vitro and in vivo models.
- Endogenous peptide presentation by MHC class I was unaffected by IRAP deficiency.
Conclusions:
- IRAP is crucial for efficient cross-presentation, acting in endosomal compartments for final peptide trimming.
- Two distinct pathways for proteasome-dependent cross-presentation are proposed: one involving IRAP in endosomes and another using endoplasmic reticulum-resident aminopeptidases.
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