PMID- 22238454 OWN - NLM STAT- MEDLINE DCOM- 20120326 LR - 20201222 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 188 IP - 4 DP - 2012 Feb 15 TI - Conventional dendritic cells require IRAP-Rab14 endosomes for efficient cross-presentation. PG - 1840-6 LID - 10.4049/jimmunol.1101504 [doi] AB - Dendritic cells (DCs) use cellular pathways collectively referred to as cross-presentation to stimulate CD8(+) T cells with peptide Ags derived from internalized, exogenous Ags. We have recently reported that DCs rely on aminoterminal trimming of cross-presented peptides by insulin-responsive aminopeptidase (IRAP), an enzyme localized in a regulated endosomal storage compartment. Considering a report contending that this role is limited to inflammatory DCs (Segura et al. 2009. Proc. Natl. Acad. Sci. USA 106: 20377-20381), in this study, we examined the role of IRAP in steady-state DC subpopulations. Steady-state conventional DCs (cDCs) and plasmacytoid DCs expressed similar amounts of IRAP. IRAP colocalized with the endosomal markers Rab14 and syntaxin 6, both known to be associated with regulated endosomal storage compartments, in CD8(+) and CD8(-) cDCs-however, to a greater extent in the former population. Likewise, IRAP recruitment to phagosomes was significantly stronger in CD8(+) DCs. IRAP deficiency compromised cross-presentation of soluble and particulate Ag by both CD8(+) and CD8(-) cDCs, again with a stronger effect in the former population. Thus, the requirement of IRAP in cross-presentation extends to steady-state cDCs. Moreover, these data suggest that increased recruitment of an IRAP(+)/Rab14(+) compartment to Ag-containing vesicles contributes to the superior cross-presentation efficacy of CD8(+) cDCs. FAU - Weimershaus, Mirjana AU - Weimershaus M AD - INSERM, Unite 1013, Paris 75015, France. FAU - Maschalidi, Sophia AU - Maschalidi S FAU - Sepulveda, Fernando AU - Sepulveda F FAU - Manoury, Benedicte AU - Manoury B FAU - van Endert, Peter AU - van Endert P FAU - Saveanu, Loredana AU - Saveanu L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120111 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Qa-SNARE Proteins) RN - EC 3.4.11.3 (Cystinyl Aminopeptidase) RN - EC 3.4.11.3 (leucyl-cystinyl aminopeptidase) RN - EC 3.6.1.- (Rab14 protein, mouse) RN - EC 3.6.5.2 (rab GTP-Binding Proteins) SB - IM MH - Animals MH - Antigen Presentation MH - CD8-Positive T-Lymphocytes/immunology/metabolism MH - Cells, Cultured MH - *Cross-Priming MH - Cystinyl Aminopeptidase/biosynthesis/*metabolism MH - Dendritic Cells/*immunology/metabolism MH - Endosomes/*immunology/metabolism MH - Mice MH - Mice, Knockout MH - Phagosomes/immunology/metabolism MH - Qa-SNARE Proteins/metabolism MH - rab GTP-Binding Proteins/*metabolism EDAT- 2012/01/13 06:00 MHDA- 2012/03/27 06:00 CRDT- 2012/01/13 06:00 PHST- 2012/01/13 06:00 [entrez] PHST- 2012/01/13 06:00 [pubmed] PHST- 2012/03/27 06:00 [medline] AID - jimmunol.1101504 [pii] AID - 10.4049/jimmunol.1101504 [doi] PST - ppublish SO - J Immunol. 2012 Feb 15;188(4):1840-6. doi: 10.4049/jimmunol.1101504. Epub 2012 Jan 11.