TY - JOUR
T1 - IRAP Identifies an Endosomal Compartment Required for MHC Class I Cross-Presentation
AU - Saveanu, Loredana
AU - Carroll, Oliver
AU - Weimershaus, Mirjana
AU - Guermonprez, Pierre
AU - Firat, Elke
AU - Lindo, Vivian
AU - Greer, Fiona
AU - Davoust, Jean
AU - Kratzer, Roland
AU - Keller, Susanna R.
AU - Niedermann, Gabriele
AU - van Endert, Peter
PY - 2009/7/10
Y1 - 2009/7/10
N2 - Major histocompatibility complex (MHC) class I molecules present peptides, produced through cytosolic proteasomal degradation of cellular proteins, to cytotoxic T lymphocytes. In dendritic cells, the peptides can also be derived from internalized antigens through a process known as cross-presentation. The cellular compartments involved in cross-presentation remain poorly defined. We found a role for peptide trimming by insulin-regulated aminopeptidase (IRAP) in cross-presentation. In human dendritic cells, IRAP was localized to a Rab14(+) endosomal storage compartment in which it interacted with MHC class I molecules. IRAP deficiency compromised cross-presentation in vitro and in vivo but did not affect endogenous presentation. We propose the existence of two pathways for proteasome-dependent cross-presentation in which final peptide trimming involves IRAP in endosomes and involves the related aminopeptidases in the endoplasmic reticulum.
AB - Major histocompatibility complex (MHC) class I molecules present peptides, produced through cytosolic proteasomal degradation of cellular proteins, to cytotoxic T lymphocytes. In dendritic cells, the peptides can also be derived from internalized antigens through a process known as cross-presentation. The cellular compartments involved in cross-presentation remain poorly defined. We found a role for peptide trimming by insulin-regulated aminopeptidase (IRAP) in cross-presentation. In human dendritic cells, IRAP was localized to a Rab14(+) endosomal storage compartment in which it interacted with MHC class I molecules. IRAP deficiency compromised cross-presentation in vitro and in vivo but did not affect endogenous presentation. We propose the existence of two pathways for proteasome-dependent cross-presentation in which final peptide trimming involves IRAP in endosomes and involves the related aminopeptidases in the endoplasmic reticulum.
U2 - 10.1126/science.1172845
DO - 10.1126/science.1172845
M3 - Article
SN - 1095-9203
VL - 325
SP - 213
EP - 217
JO - Science
JF - Science
IS - 5937
ER -