The GTPase Rab3b/3c-positive recycling vesicles are involved in cross-presentation in dendritic cells

Zou, Liyun; Zhou, Jingran; Zhang, Jinyu; Li, Jingyi; Liu, Na; Chai, Linlin; Li, Na; Liu, Ting; Li, Liqi; Xie, Zhiqin; Liu, Hongli; Wan, Ying; Wu, Yuzhang

doi:10.1073/pnas.0905684106

Cited by 52 publications

(39 citation statements)

References 48 publications

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“…Peptide-loaded MHC II is transported to the cell surface for presentation to CD4+ T cells (Figure 1a). In the cross-presentation pathway, exogenously derived peptides are presented in the context of MHC I, as phagocytized bacterial antigenic peptides are loaded onto phagosomal MHC I, which is recycled from the cell surface (Figure 1b) [21], [25], [26]. The relative importance and functionality of this alternative pathway in mammals is still debated [21], [27].…”

Section: Introductionmentioning

confidence: 99%

Unraveling the Evolution of the Atlantic Cod’s (Gadus morhua L.) Alternative Immune Strategy

et al. 2013

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Genes encoding the major histocompatibility complex (MHC) have been thought to play a vital role in the adaptive immune system in all vertebrates. The discovery that Atlantic cod (Gadus morhua) has lost important components of the MHC II pathway, accompanied by an unusually high number of MHC I genes, shed new light on the evolution and plasticity of the immune system of teleosts as well as in higher vertebrates. The overall aim of this study was to further investigate the highly expanded repertoire of MHC I genes using a cDNA approach to obtain sequence information of both the binding domains and the sorting signaling potential in the cytoplasmic tail. Here we report a novel combination of two endosomal sorting motifs, one tyrosine-based associated with exogenous peptide presentation by cross-presenting MHCI molecules, and one dileucine-based associated with normal MHC II functionality. The two signal motifs were identified in the cytoplasmic tail in a subset of the genes. This indicates that these genes have evolved MHC II-like functionality, allowing a more versatile use of MHC I through cross-presentation. Such an alternative immune strategy may have arisen through adaptive radiation and acquisition of new gene function as a response to changes in the habitat of its ancestral lineage.

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Section: Introductionmentioning

confidence: 99%

Unraveling the Evolution of the Atlantic Cod’s (Gadus morhua L.) Alternative Immune Strategy

et al. 2013

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“…While NOX2 and Rac2 also regulate phagosomal acidification in CD8 + cDCs (Savina et al, 2009), only NOX2, but not Rac2, deficiency reduced CD8 + cDC cross-presentation of soluble antigen. Rab11a (Nair-Gupta et al, 2014), Rab3b (Zou et al, 2009) and Sec22b (Cebrian et al, 2011), which regulate vesicular trafficking, were shown to promote cross-presentation, but were studied using BM cultures treated with GM-CSF or in the DC2.4 cell line. In our studies, Mo-DCs generated with GM-CSF alone were relatively inefficient in cross-priming of cell-associated antigen compared with CD8 + cDCs and Mo-DCs generated with both GM-CSF and IL-4 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte-Derived Dendritic Cells

et al. 2016

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Summary Both classical DCs (cDCs) and monocyte-derived DCs (Mo-DCs) are capable of cross-priming CD8+ T cells in response to cell-associated antigens. We found that Ly-6ChiTREML4− monocytes can differentiate into Zbtb46+ Mo-DCs in response to GM-CSF and IL-4, but that Ly-6ChiTREML4+ monocytes were committed to differentiate into Ly-6CloTREML4+ monocytes. Differentiation of Zbtb46+ Mo-DCs capable of efficient cross-priming required both GM-CSF and IL-4, and was accompanied by induction of Batf3 and Irf4. However, monocytes require IRF4, but not BATF3, to differentiate into Zbtb46+ Mo-DCs capable of cross-priming CD8+ T cells. Instead, Irf4−/− monocytes differentiate into macrophages in response to GM-CSF and IL-4. Thus, cDCs and Mo-DCs require distinct transcriptional programs of differentiation in acquiring the capacity to prime CD8+ T cells. These differences may be of consideration in the use of therapeutic DC vaccines based on Mo-DCs.

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“…The isoform Rab3C was originally detected in one of the first phagosomal proteomes 11 and recently in phagosomes isolated from IFN-γ activated cells 14 . In a lentivirus-based siRNA screening, Rab3B/C was found to be required for antigen cross-presentation in dendritic cells 90 . Based on these observations, it is proposed that in dendritic cells, internalized bacteria in phagosomes and Rab3B/C-positive recycling endosomes may constitute an exocytic step of cross-presentation 90 …”

Section: Rab Gtpases Less Often Identified In Phagosomes and With Uncmentioning

confidence: 99%

Functional role(s) of phagosomal Rab GTPases

Gutierrez

2013

Small GTPases

102

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Rab GTPases are at the central node of the machinery that regulates trafficking of organelles, including phagosomes. Thanks to the unique combination of high quality phagosome purification with highly sensitive proteomic studies, the network of Rab proteins that are dynamically associated with phagosomes during the process of maturation of this organelle is relatively well known. Whereas the phagosomal functions of many of the Rab proteins associated with phagosomes are characterized, the role(s) of most of these trafficking regulators remain to be identified. In some cases, even when the function in the context of phagosome biology is described, phagosomal Rab proteins seem to have similar roles. This review summarizes the current knowledge about the identity and function of phagosomal Rab GTPases, with a particular emphasis on new evidence that clarify these seemingly overlapping Rab functions during phagosome maturation.

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The GTPase Rab3b/3c-positive recycling vesicles are involved in cross-presentation in dendritic cells

Cited by 52 publications

References 48 publications

Unraveling the Evolution of the Atlantic Cod’s (Gadus morhua L.) Alternative Immune Strategy

Unraveling the Evolution of the Atlantic Cod’s (Gadus morhua L.) Alternative Immune Strategy

Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte-Derived Dendritic Cells

Functional role(s) of phagosomal Rab GTPases

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