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A role for lipid bodies in the cross-presentation of phagocytosed antigens by MHC class I in dendritic cells

Bougneres, Laurence
Helft, Julie
Tiwari, Sangeeta
Vargas, Pablo
Chang, Benny Hung-Junn
Chan, Lawrence
Campisi, Laura
Lauvau, Gregoire
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Published in Immunity. 2009, vol. 31, no. 2, p. 232-244
Abstract 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.
Keywords AnimalsAntigen Presentation/*immunologyCD4-Positive T-Lymphocytes/immunologyCD8-Positive T-Lymphocytes/immunology*Cross-PrimingDendritic Cells/*immunologyEndoplasmic Reticulum/immunologyGTP Phosphohydrolases/genetics/immunology/metabolismHistocompatibility Antigens Class I/*immunologyLipids/*immunologyMembrane Proteins/genetics/immunology/metabolismMiceMice, KnockoutMice, Transgenic*Phagocytosis
PMID: 19699172
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Research group Pathologie et immunologie (906)
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BOUGNERES, Laurence et al. A role for lipid bodies in the cross-presentation of phagocytosed antigens by MHC class I in dendritic cells. In: Immunity, 2009, vol. 31, n° 2, p. 232-244. doi: 10.1016/j.immuni.2009.06.022 https://archive-ouverte.unige.ch/unige:19703

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Deposited on : 2012-04-23

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