A Role for Lipid Bodies in the Cross-presentation of Phagocytosed Antigens by MHC Class I in Dendritic Cells
| Autor: | Benny Hung-Junn Chang, Grégoire Lauvau, Pierre Guermonprez, Stéphanie Hugues, Julie Helft, Ana Maria Lennon Dumenil, Michel C. Nussenzweig, Pradeep Kumar, Sebastian Amigorena, Pablo Vargas, Lawrence Chan, Sangeeta Tiwari, Laurence Bougnères, Laura Campisi, John D. MacMicking, Alice O. Kamphorst |
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| Rok vydání: | 2009 |
| Předmět: |
Dendritic Cells/*immunology
CD4-Positive T-Lymphocytes Cross-Priming Perilipin 2 Antigen presentation Immunology Mice Transgenic ddc:616.07 Membrane Proteins/genetics/immunology/metabolism CD8-Positive T-Lymphocytes CD8-Positive T-Lymphocytes/immunology Major histocompatibility complex Endoplasmic Reticulum Lipids/*immunology Perilipin-2 GTP Phosphohydrolases 03 medical and health sciences Mice 0302 clinical medicine Antigen Phagocytosis MHC class I Histocompatibility Antigens Class I/*immunology Animals Immunology and Allergy Antigen Presentation/*immunology MOLIMMUNO 030304 developmental biology Mice Knockout 0303 health sciences Antigen Presentation biology Antigen processing Histocompatibility Antigens Class I Cross-presentation Membrane Proteins Dendritic Cells Lipids Cell biology Endoplasmic Reticulum/immunology Infectious Diseases CELLIMMUNO CD4-Positive T-Lymphocytes/immunology biology.protein GTP Phosphohydrolases/genetics/immunology/metabolism CD8 030215 immunology |
| Zdroj: | Immunity, Vol. 31, No 2 (2009) pp. 232-244 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2009.06.022 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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