Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells

Kleijmeer, Monique J.; Ramm, Georg; Schuurhuis, Danita H.; Griffith, Janice; Rescigno, María; Ricciardi‐Castagnoli, Paola; Rudensky, Alexander Y.; Ossendorp, Ferry; Melief, Cornelis J.M.; Stoorvogel, Willem; Geuze, Hans J.

doi:10.1083/jcb.200103071

Cited by 258 publications

(275 citation statements)

References 64 publications

(92 reference statements)

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“…DC maturation-associated reorganization of lysosomes has been noted previously in a murine DC line and may account for efficient transport of MHC class II molecules from lysosomes to the plasma membrane during DC maturation (39). In human monocyte-derived DCs analyzed in the present study we also observed that lysosomes are deprived of MHC class II after maturation and loose their tightly packed membranes (Fig.…”

Section: Discussionsupporting

confidence: 85%

“…Three pathways of delivery from lysosomes to the plasma membrane have been described. Tubulation and vesicle formation of the lysosome were proposed to account for delivery of MHC class II molecules to the plasma membrane during DC maturation (39). Previously, a specialized CIIV vesicle was identified in murine DC and was also proposed as a delivery route for MHC class II during DC maturation (7).…”

Section: Discussionmentioning

confidence: 99%

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CD1 Molecules Efficiently Present Antigen in Immature Dendritic Cells and Traffic Independently of MHC Class II During Dendritic Cell Maturation

Cao

Sugita

Wel

et al. 2002

The Journal of Immunology

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Upon exposure to Ag and inflammatory stimuli, dendritic cells (DCs) undergo a series of dynamic cellular events, referred to as DC maturation, that involve facilitated peptide Ag loading onto MHC class II molecules and their subsequent transport to the cell surface. Besides MHC molecules, human DCs prominently express molecules of the CD1 family (CD1a, -b, -c, and -d) and mediate CD1-dependent presentation of lipid and glycolipid Ags to T cells, but the impact of DC maturation upon CD1 trafficking and Ag presentation is unknown. Using monocyte-derived immature DCs and those stimulated with TNF-α for maturation, we observed that none of the CD1 isoforms underwent changes in intracellular trafficking that mimicked MHC class II molecules during DC maturation. In contrast to the striking increase in surface expression of MHC class II on mature DCs, the surface expression of CD1 molecules was either increased only slightly (for CD1b and CD1c) or decreased (for CD1a). In addition, unlike MHC class II, DC maturation-associated transport from lysosomes to the plasma membrane was not readily detected for CD1b despite the fact that both molecules were prominently expressed in the same MIIC lysosomal compartments before maturation. Consistent with this, DCs efficiently presented CD1b-restricted lipid Ags to specific T cells similarly in immature and mature DCs. Thus, DC maturation-independent pathways for lipid Ag presentation by CD1 may play a crucial role in host defense, even before DCs are able to induce maximum activation of peptide Ag-specific T cells.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

CD1 Molecules Efficiently Present Antigen in Immature Dendritic Cells and Traffic Independently of MHC Class II During Dendritic Cell Maturation

Cao

Sugita

Wel

et al. 2002

The Journal of Immunology

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“…In maturing DCs, transport of MHCII is mediated via membrane tubules that radiate out from the MIIC toward the plasma membrane, and this pathway depends on an intact microtubule network (Kleijmeer et al 2001;Boes et al 2002Boes et al , 2003Chow et al 2002;Vyas et al 2007;van Nispen tot Pannerden et al 2010). MHCII, DM, and LAMP1 are not enriched in these tubules relative to the vacuolar endosomes from which they derive, suggesting that this pathway may not require active recruitment but is entered by default (Kleijmeer et al 2001).…”

Section: Trafficking Of Pmhciimentioning

confidence: 99%

“…In professional antigen-presenting cells, the organelles at which MHCII peptide loading occurs mainly constitute late endosomes, although lysosomes have also been implicated (Geuze 1998). Together, these endocytic compartments are also referred to as MHCII compartments (MIICs) (Peters et al 1991;Kleijmeer et al 1997Kleijmeer et al , 2001). DCs constitutively synthesize MHCII, which, in the absence of pathogen, are all loaded with "self " peptides in MIICs.…”

mentioning

confidence: 99%

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

Broeke

Wubbolts

Stoorvogel

2013

Cold Spring Harbor Perspectives in Biology

143

102

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For the initiation of adaptive immune responses, dendritic cells present antigenic peptides in association with major histocompatibility complex class II (MHCII) to naïve CD4 þ T lymphocytes. In this review, we discuss how antigen presentation is regulated through intracellular processing and trafficking of MHCII. Newly synthesized MHCII is chaperoned by the invariant chain to endosomes, where peptides from endocytosed pathogens can bind. In nonactivated dendritic cells, peptide-loaded MHCII is ubiquitinated and consequently sorted by the ESCRT machinery to intraluminal vesicles of multivesicular bodies, ultimately leading to lysosomal degradation. Ubiquitination of newly synthesized MHCII is blocked when dendritic cells are activated, now allowing its transfer to the cell surface. This mode of regulation for MHCII is a prime example of how molecular processing and sorting at multivesicular bodies can determine the expression of signaling receptors at the plasma membrane.

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“…In eukaryotic cells, the MVB pathway controls various important processes such as receptor down-regulation, antigen presentation, cytokinesis, retroviral budding, and autophagy (1)(2)(3)(4)(5)(6). In the budding yeast Saccharomyces cerevisiae, previous studies identified a number of genes involved in vacuolar protein sorting (VPS) (7,8).…”

mentioning

confidence: 99%

The Endosomal Na+/H+ Exchanger Contributes to Multivesicular Body Formation by Regulating the Recruitment of ESCRT-0 Vps27p to the Endosomal Membrane

Mitsui

Koshimura

Yoshikawa

et al. 2011

Journal of Biological Chemistry

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Multivesicular bodies (MVBs) are late endosomal compartments containing luminal vesicles (MVB vesicles) that are formed by inward budding of the endosomal membrane. In budding yeast, MVBs are an important cellular mechanism for the transport of membrane proteins to the vacuolar lumen. This process requires a class E subset of vacuolar protein sorting (VPS) genes. VPS44 (allelic to NHX1) encodes an endosomelocalized Na ؉ /H ؉ exchanger. The function of the VPS44 exchanger in the context of vacuolar protein transport is largely unknown. Using a cell-free MVB formation assay system, we demonstrated that Nhx1p is required for the efficient formation of MVB vesicles in the late endosome. The recruitment of Vps27p, a class E Vps protein, to the endosomal membrane was dependent on Nhx1p activity and was enhanced by an acidic pH at the endosomal surface. Taken together, we propose that Nhx1p contributes to MVB formation by the recruitment of Vps27p to the endosomal membrane, possibly through Nhx1p antiporter activity.Multivesicular bodies (MVBs) 3 are a subset of late endosomes that contain internal vesicles, permitting precursor and plasma membrane proteins to reach the lysosome or vacuole lumen for degradation or maturation, respectively. In eukaryotic cells, the MVB pathway controls various important processes such as receptor down-regulation, antigen presentation, cytokinesis, retroviral budding, and autophagy (1-6). In the budding yeast Saccharomyces cerevisiae, previous studies identified a number of genes involved in vacuolar protein sorting (VPS) (7,8). These Vps proteins function at distinct steps of protein transport between the Golgi complex and the vacuole (7,8). A subset of Vps proteins, class E proteins, is involved in MVB formation. Most class E proteins are components of five distinct complexes; Vps27p-Hse1p (also called endosomal sorting complexes required for transport-0 (ESCRT-0), -I, -II, and -III and Vps4p. These complexes are required for the formation of internal vesicles and sorting of cargo proteins to the vesicles from the endosomal membrane (3, 9). Vps27p (ESCRT-0) recruits ESCRT-I, which in turn recruits and/or activates ESCRT-II and ESCRT-III at the endosome (3, 10). Recent in vitro studies have provided new insights into the precise role of each ESCRT complex in MVB formation (11-13). ESCRT-0 initiates the MVB sorting process by recruiting ESCRT-I to the endosomal membrane and concentrating ubiquitylated MVB cargos to the vesicle budding site (12). ESCRT-I and ESCRT-II are directly involved in membrane budding by stabilizing the bud necks, whereas ESCRT-III is responsible for the cleavage of bud necks (11-13). Finally, the AAA-type ATPase Vps4p dissociates the ESCRT-III complex from the endosome (14). The sequential activity of these complexes on the cytoplasmic surface of endosomes directs the budding and fission of vesicles into the lumen of the endosome and the sequestration of cargo proteins in the vesicle. Defects in ESCRT proteins prevent internal vesicle formation and result in exagg...

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Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells

Cited by 258 publications

References 64 publications

CD1 Molecules Efficiently Present Antigen in Immature Dendritic Cells and Traffic Independently of MHC Class II During Dendritic Cell Maturation

CD1 Molecules Efficiently Present Antigen in Immature Dendritic Cells and Traffic Independently of MHC Class II During Dendritic Cell Maturation

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

The Endosomal Na+/H+ Exchanger Contributes to Multivesicular Body Formation by Regulating the Recruitment of ESCRT-0 Vps27p to the Endosomal Membrane

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