A CD74-dependent MHC class I endolysosomal cross-presentation pathway

Basha, Genc; Omilusik, Kyla; Chávez-Steenbock, Ana; Reinicke, Anna T.; Lack, Nathan A.; Choi, Kyung Bok; Jefferies, Wilfred A.

doi:10.1038/ni.2225

Cited by 114 publications

(110 citation statements)

References 51 publications

(81 reference statements)

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“…Three groups reported that Ags delivered via the mannose receptor were routed into early endosomes resulting in more efficient cross-presentation. 9,44,46 In contrast, we observed that mannose NPs were not routed into early but rather into acidic endosomes, which did not interfere with cross-presentation of the epitope HER2/neu 369-377 . Actually, our studies showed that some degree of acidification was crucial for the generation of the peptide HER2/neu 369-377 , which is compatible with antigen processing by cathepsins that are activated at low pH.…”

Section: Discussioncontrasting

confidence: 45%

“…According to some reports, antigen for cross-presentation needed to be routed into non-acidified compartments and acidification prevented or decreased cross-presentation. 44,45 We found efficient cross-presentation in both situations. Three groups reported that Ags delivered via the mannose receptor were routed into early endosomes resulting in more efficient cross-presentation.…”

Section: Discussionmentioning

confidence: 69%

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Spatial separation of the processing and MHC class I loading compartments for cross-presentation of the tumor-associated antigen HER2/neuby human dendritic cells

et al. 2015

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(2015) Spatial separation of the processing and MHC class I loading compartments for cross-presentation of the tumor-associated antigen HER2/neu by human dendritic cells, OncoImmunology, 4:11, e1047585, DOI: 10.1080/2162402X.2015 Cross-presentation is the process by which professional antigen presenting cells (APCs) (B cells, dendritic cells (DCs) and macrophages) present endocytosed antigens (Ags) via MHC-I to CD8C T cells. This process is crucial for induction of adaptive immune responses against tumors and infected cells. The pathways and cellular compartments involved in cross-presentation are unresolved and controversial. Among the cells with cross-presenting capacity, DCs are the most efficient, which was proposed to depend on prevention of endosomal acidification to block degradation of the epitopes. Contrary to this view, we show in this report that some cargoes induce strong endosomal acidification following uptake by human DCs, while others not. Moreover, processing of the tumor-associated antigen HER2/neu delivered in nanoparticles (NP) for cross-presentation of the epitope HER2/neu 369-377 on HLA-A2 depended on endosomal acidification and cathepsin activity as well as proteasomes, and newly synthesized HLA class I. However, the HLA-A*0201/HER2/neu 369-377 complexes were not found in the endoplasmic reticulum (ER) nor in endolysosomes but in hitherto not described vesicles. The data thus indicate spatial separation of antigen processing and loading of MHC-I for cross-presentation: antigen processing occurs in the uptake compartment and the cytosol whereas MHC-I loading with peptide takes place in a distinct subcellular compartment. The findings further elucidate the cellular pathways involved in the cross-presentation of a full-length, clinically relevant tumor-associated antigen by human DCs, and the impact of the vaccine formulation on antigen processing and CD8 + T cell induction.

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Section: Discussioncontrasting

confidence: 45%

Section: Discussionmentioning

confidence: 69%

Spatial separation of the processing and MHC class I loading compartments for cross-presentation of the tumor-associated antigen HER2/neuby human dendritic cells

et al. 2015

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“…by guest www.bloodjournal.org From early endosomes, 33,40 late endosomes or endo/lysosomes. [41][42][43] These phagosomes contain MHCI loading complex components. 36,37,40,44,45 To clarify mechanisms involved in BDCA-3 ϩ DC crosspresentation, we tested the involvement of endosomal and proteasomal processing, analogous to experiments described in Figure 2.…”

Section: Differential Antigen Uptake Does Not Explain Increased Crossmentioning

confidence: 99%

Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells

Flinsenberg¹,

Compeer²,

Koning

et al. 2012

Blood

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The reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3 ؉ (CD141 ؉ ) subset DCs may be particularly effective in DC vaccination trials. BDCA-3 ؉ DCs had however been mostly characterized for their ability to cross-present antigen from necrotic cells. We here describe our study of human BDCA-3 ؉ DCs in elicitation of HCMV-specific CD8 ؉ T-cell clones.

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“…Powis (2006) reported that the CLIP region is directly involved in the association of Ii with MHC class I molecules, and that this can result in the inclusion of Ii in the MHC class I peptide-loading complex. Recent research showed that Ii associated with MHC class I in the endoplasmic reticulum of DCs and mediated trafficking of MHC class I to endolysosomal compartments for loading with exogenous peptides (Basha et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Intracellular localization and association of MHC class I with porcine invariant chain

Xu¹,

Wu²,

Yu³

2013

Genet. Mol. Res.

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ABSTRACT. The objective was to investigate the intracellular localization and association of pig major histocompatibility complex (MHC) class I subunits with invariant chain (Ii). Pig MHC class I subunit cDNAs were cloned by RT-PCR and eukaryotic expression plasmids of α and β2m were constructed with fusions to red or enhanced green fluorescent protein (pDsRed2-N1-α, pEGFP-N1-α, pDsRed2-N1-β2m, and pEGFP-N1-β2m). A pig Ii mutant with a deleted CLIP region (DCLIP-Ii) was constructed by overlap extension PCR. Wild-type Ii and mutant Ii were cloned into pEGFP-C1 (pEGFP-C1-Ii, pEGFP-C1-DCLIP-Ii). The recombinant plasmids of MHC I subunits and pEGFP-C1-Ii (pEGFP-C1-DCLIP-Ii) were transiently cotransfected into COS-7 cells with Lipofectamine 2000. Immunofluorescence microscopy was performed to detect expression and intracellular localization of Ii and MHC I subunits, and immunoprecipitation was used to analyze their association. Our results indicated that pig Ii associates with integrated MHC I subunits to form oligomers, but cannot associate with single MHC I subunits. Furthermore, deletion of the Ii CLIP sequence blocks association with integrated MHC I subunits. Thus, pig Ii cannot associate with a single MHC I molecule, the α or β2m chain, but Ii and the integrated MHC I molecule can form complexes that colocalize in

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A CD74-dependent MHC class I endolysosomal cross-presentation pathway

Cited by 114 publications

References 51 publications

Spatial separation of the processing and MHC class I loading compartments for cross-presentation of the tumor-associated antigen HER2/neuby human dendritic cells

Spatial separation of the processing and MHC class I loading compartments for cross-presentation of the tumor-associated antigen HER2/neuby human dendritic cells

Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells

Intracellular localization and association of MHC class I with porcine invariant chain

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