Bougnères Laurence, Helft Julie, Tiwari Sangeeta, Vargas Pablo, Chang Benny Hung-Junn, Chan Lawrence, Campisi Laura, Lauvau Gregoire, Hugues Stephanie, Kumar Pradeep, Kamphorst Alice O, Dumenil Ana-Maria Lennon, Nussenzweig Michel, MacMicking John D, Amigorena Sebastian, Guermonprez Pierre
INSERM U653, Institut Curie, Section Recherche, 26, rue d'Ulm, 75248 Paris, Cedex 05, France.
Immunity. 2009 Aug 21;31(2):232-44. doi: 10.1016/j.immuni.2009.06.022.
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.
树突状细胞（DCs）具有显著的能力，能够将与主要组织相容性复合体（MHC）I类相关的外源性抗原交叉呈递给CD8(+) T细胞。然而，交叉呈递背后的细胞内途径仍不清楚。目前的模型涉及蛋白酶体对抗原的胞质蛋白水解以及通过与抗原加工相关的转运体（TAP1和TAP2）将肽导入内质网（ER）或吞噬体腔。在这里，我们表明DCs表达一种内质网驻留的47 kDa免疫相关GTP酶，Igtp（Irgm3）。Igtp定位于内质网和脂质体（LB）膜上，在那里它与LB包被成分ADFP结合。编码Igtp或ADFP的基因失活导致DCs中LB形成缺陷，并严重损害吞噬抗原向CD8(+) T细胞的交叉呈递，但不影响向CD4(+) T细胞的抗原呈递。因此，我们确定了LB细胞器在调节DCs中外源性抗原向CD8(+) T淋巴细胞的交叉呈递中的新作用。
