PMID- 19699172 OWN - NLM STAT- MEDLINE DCOM- 20090925 LR - 20211020 IS - 1097-4180 (Electronic) IS - 1074-7613 (Print) IS - 1074-7613 (Linking) VI - 31 IP - 2 DP - 2009 Aug 21 TI - A role for lipid bodies in the cross-presentation of phagocytosed antigens by MHC class I in dendritic cells. PG - 232-44 LID - 10.1016/j.immuni.2009.06.022 [doi] AB - Dendritic cells (DCs) have the striking ability to cross-present exogenous antigens in association with major histocompatibility complex (MHC) class I to CD8(+) T cells. However, the intracellular pathways underlying cross-presentation remain ill defined. Current models involve cytosolic proteolysis of antigens by the proteasome and peptide import into endoplasmic reticulum (ER) or phagosomal lumen by the transporters associated with antigen processing (TAP1 and TAP2). Here, we show that DCs expressed an ER-resident 47 kDa immune-related GTPase, Igtp (Irgm3). Igtp resides on ER and lipid body (LB) membranes where it binds the LB coat component ADFP. Inactivation of genes encoding for either Igtp or ADFP led to defects in LB formation in DCs and severely impaired cross-presentation of phagocytosed antigens to CD8(+) T cells but not antigen presentation to CD4(+) T cells. We thus define a new role for LB organelles in regulating cross-presentation of exogenous antigens to CD8(+) T lymphocytes in DCs. FAU - Bougneres, Laurence AU - Bougneres L AD - INSERM U653, Institut Curie, Section Recherche, 26, rue d'Ulm, 75248 Paris, Cedex 05, France. FAU - Helft, Julie AU - Helft J FAU - Tiwari, Sangeeta AU - Tiwari S FAU - Vargas, Pablo AU - Vargas P FAU - Chang, Benny Hung-Junn AU - Chang BH FAU - Chan, Lawrence AU - Chan L FAU - Campisi, Laura AU - Campisi L FAU - Lauvau, Gregoire AU - Lauvau G FAU - Hugues, Stephanie AU - Hugues S FAU - Kumar, Pradeep AU - Kumar P FAU - Kamphorst, Alice O AU - Kamphorst AO FAU - Dumenil, Ana-Maria Lennon AU - Dumenil AM FAU - Nussenzweig, Michel AU - Nussenzweig M FAU - MacMicking, John D AU - MacMicking JD FAU - Amigorena, Sebastian AU - Amigorena S FAU - Guermonprez, Pierre AU - Guermonprez P LA - eng GR - R01 HL051586/HL/NHLBI NIH HHS/United States GR - R01 AI068041-01A1/AI/NIAID NIH HHS/United States GR - P01 AI051573-070004/AI/NIAID NIH HHS/United States GR - R01 AI068041/AI/NIAID NIH HHS/United States GR - P01 AI051573/AI/NIAID NIH HHS/United States GR - HL 51586/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Lipids) RN - 0 (Membrane Proteins) RN - 0 (Perilipin-2) RN - 0 (Plin2 protein, mouse) RN - EC 3.6.1.- (GTP Phosphohydrolases) RN - EC 3.6.1.- (Igtp protein, mouse) SB - IM CIN - Immunity. 2009 Aug 21;31(2):176-8. PMID: 19699167 MH - Animals MH - Antigen Presentation/*immunology MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - *Cross-Priming MH - Dendritic Cells/*immunology MH - Endoplasmic Reticulum/immunology MH - GTP Phosphohydrolases/genetics/immunology/metabolism MH - Histocompatibility Antigens Class I/*immunology MH - Lipids/*immunology MH - Membrane Proteins/genetics/immunology/metabolism MH - Mice MH - Mice, Knockout MH - Mice, Transgenic MH - Perilipin-2 MH - *Phagocytosis PMC - PMC2803012 MID - NIHMS136509 COIS- The authors have no conflicting financial interests. EDAT- 2009/08/25 09:00 MHDA- 2009/09/26 06:00 PMCR- 2010/08/21 CRDT- 2009/08/25 09:00 PHST- 2009/04/29 00:00 [received] PHST- 2009/06/13 00:00 [revised] PHST- 2009/06/18 00:00 [accepted] PHST- 2009/08/25 09:00 [entrez] PHST- 2009/08/25 09:00 [pubmed] PHST- 2009/09/26 06:00 [medline] PHST- 2010/08/21 00:00 [pmc-release] AID - S1074-7613(09)00325-2 [pii] AID - 10.1016/j.immuni.2009.06.022 [doi] PST - ppublish SO - Immunity. 2009 Aug 21;31(2):232-44. doi: 10.1016/j.immuni.2009.06.022.