IRAP Identifies an Endosomal Compartment Required for MHC Class I Cross-Presentation

被引：205

作者：

Saveanu, Loredana ^{[1
,2
]}

Carroll, Oliver ^{[1
,2
]}

Weimershaus, Mirjana ^{[1
,2
]}

Guermonprez, Pierre ^{[3
,4
]}

Firat, Elke ^{[5
]}

Lindo, Vivian ^{[6
]}

Greer, Fiona ^{[6
]}

Davoust, Jean ^{[1
,2
]}

Kratzer, Roland ^{[1
,2
]}

Keller, Susanna R. ^{[7
]}

Niedermann, Gabriele ^{[5
]}

van Endert, Peter ^{[1
,2
]}

机构：

[1] INSERM, U580, F-75015 Paris, France

[2] Univ Paris 05, Fac Med Rene Descartes, F-75015 Paris, France

[3] INSERM, U653, F-75006 Paris, France

[4] Inst Curie, Ctr Rech, F-75006 Paris, France

[5] Univ Hosp Freiburg, Clin Radiotherapy, D-79106 Freiburg, Germany

[6] M SCAN Ltd, Wokingham RG41 2TZ, Berks, England

[7] Univ Virginia, Dept Internal Med, Div Endocrinol, Charlottesville, VA 22908 USA

来源：

SCIENCE | 2009年 / 325卷 / 5937期

关键词：

INSULIN-REGULATED AMINOPEPTIDASE; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; DENDRITIC CELLS; PEPTIDES; CROSSPRESENTATION; GLUT4; MOLECULES; NETWORK; PATHWAY;

D O I：

10.1126/science.1172845

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：213 / 217

页数：5

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