Publication Date:
2009-06-06
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saveanu, Loredana -- Carroll, Oliver -- Weimershaus, Mirjana -- Guermonprez, Pierre -- Firat, Elke -- Lindo, Vivian -- Greer, Fiona -- Davoust, Jean -- Kratzer, Roland -- Keller, Susanna R -- Niedermann, Gabriele -- van Endert, Peter -- New York, N.Y. -- Science. 2009 Jul 10;325(5937):213-7. doi: 10.1126/science.1172845. Epub 2009 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM, U580, 75015 Paris, France; Universite Paris Descartes, Faculte de Medecine Rene Descartes, 75015 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19498108" target="_blank"〉PubMed〈/a〉
Keywords:
Adoptive Transfer
;
Animals
;
*Antigen Presentation
;
CD8-Positive T-Lymphocytes/immunology
;
*Cross-Priming
;
Cystinyl Aminopeptidase/*metabolism
;
Dendritic Cells/enzymology/*immunology/metabolism
;
Endosomes/*enzymology
;
Epitopes
;
HLA Antigens/immunology/metabolism
;
Histocompatibility Antigens Class I/*immunology/*metabolism
;
Humans
;
Mice
;
Mice, Knockout
;
Phagocytosis
;
Phagosomes/enzymology
;
Proteasome Endopeptidase Complex/metabolism
;
Substrate Specificity
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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