TY - JOUR
T1 - A Role for Lipid Bodies in the Cross-presentation of Phagocytosed Antigens by MHC Class I in Dendritic Cells
AU - Bougnères, Laurence
AU - Helft, Julie
AU - Tiwari, Sangeeta
AU - Vargas, Pablo
AU - Chang, Benny Hung Junn
AU - Chan, Lawrence
AU - Campisi, Laura
AU - Lauvau, Gregoire
AU - Hugues, Stephanie
AU - Kumar, Pradeep
AU - Kamphorst, Alice O.
AU - Dumenil, Ana Maria Lennon
AU - Nussenzweig, Michel
AU - MacMicking, John D.
AU - Amigorena, Sebastian
AU - Guermonprez, Pierre
N1 - Funding Information:
The authors thank G. Taylor, H. Shen, Z. Maciorowski, C. Guerin, I. Grandjean, A. Boissonnas, L. Saveanu, A. Savina, W. Faigle, D. Loew, B. Lombard, C.L. Trubert, M. Merad, and S. Davis for reagents, helpful discussions, or critical reading of the manuscript. L.B. was supported by the Association pour la Recherche sur le Cancer, the Curie Institute, and INSERM. L.C. was supported by the National Institutes of Health (NIH) Grant HL 51586. J.D.M. was supported by the NIH National Institute of Allergy and Infectious Diseases (R01 AI068041-01A1), the Burroughs Wellcome Fund Award, the Searle Foundation (05-F-114), Cancer Research Institute, and the W.W. Winchester Foundation. P.G. was supported by the Centre National de la Recherche Scientifique, the Agence Nationale pour la Recherche, and the Rockefeller University.
PY - 2009/8/21
Y1 - 2009/8/21
N2 - 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.
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.
KW - CELLIMMUNO
KW - MOLIMMUNO
UR - https://www.scopus.com/pages/publications/68649128145
U2 - 10.1016/j.immuni.2009.06.022
DO - 10.1016/j.immuni.2009.06.022
M3 - Article
C2 - 19699172
AN - SCOPUS:68649128145
SN - 1074-7613
VL - 31
SP - 232
EP - 244
JO - Immunity
JF - Immunity
IS - 2
ER -