Sorting of MHC Class II Molecules into Exosomes through a Ubiquitin‐Independent Pathway

Gauvreau, Marie-Élaine; Côté, Marie-Hélène; Bourgeois-Daigneault, Marie-Claude; Rivard, Louis-David; Xiu, Fangming; Brunet, A. Gómez; Shaw, Andrew; Steimle, Viktor; Thibodeau, Jacques

doi:10.1111/j.1600-0854.2009.00948.x

Cited by 66 publications

(59 citation statements)

References 90 publications

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“…Furthermore, CD81 is important for the sorting of its associated proteins into exosomes [42]. Other studies support that the ubiquitination drives MHCIIcontaining MVBs to degradation upon fusion with the lysosomal system [52] (Fig. 1).…”

Section: Escrt-dependent and Independent Sorting Mechanisms Into Ilvsmentioning

confidence: 88%

“…Depending on the added PTMs, these receptors can have different fates. Ubiquitinated-MHC-II is preferentially directed to degradative MVBs for degradation in lysosomes, whereas, Ub-LMP2A and ph-EGFR are usually incorporated into ILVs of exocytic MVBs, which are fused with plasma membrane to be secreted as EVs [52,77,116]. In the case of acetylated-GRP78 and ISGylated-TSG101, these PTMs act as cellular retention tags, promoting their degradation in lysosomes [128,129].…”

Section: Escrt-dependent and Independent Sorting Mechanisms Into Ilvsmentioning

confidence: 99%

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Post-translational add-ons mark the path in exosomal protein sorting

Moreno-Gonzalo

Fernández-Delgado

Sánchez‐Madrid

2017

Cell. Mol. Life Sci.

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Section: Escrt-dependent and Independent Sorting Mechanisms Into Ilvsmentioning

confidence: 88%

Section: Escrt-dependent and Independent Sorting Mechanisms Into Ilvsmentioning

confidence: 99%

Post-translational add-ons mark the path in exosomal protein sorting

Moreno-Gonzalo

Fernández-Delgado

Sánchez‐Madrid

2017

Cell. Mol. Life Sci.

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“…This method has been reported to yield quantitative and reproducible results (22). Equal numbers of MJ and of MJ-gB cells were cultured in the same volume for the same time to produce exosomes.…”

Section: Release Of Gb-dr Complexes Via Exosomesmentioning

confidence: 99%

The Herpes Simplex Virus-1 Encoded Glycoprotein B Diverts HLA-DR into the Exosome Pathway

Temme

Eis‐Hübinger

McLellan

et al. 2009

The Journal of Immunology

103

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Neutralizing Abs play an important role for immunity against HSV-1 infection. This branch of the immune response is initiated by MHC class II Ag presentation and activation of T cell help. In this study, we show that the HSV-1 encoded glycoprotein B (gB) manipulates the class II processing pathway by perturbing endosomal sorting and trafficking of HLA-DR (DR) molecules. Expression of gB in the human melanoma cell line Mel JuSo results in formation of enlarged DR+ intracellular vesicles. Costaining of the vesicles revealed the presence of DR, gB, and the late endosomal marker CD63. The lumen of these late endosomal membranes shows a variable content, containing either gB or CD63, or both CD63 and gB. gB targets DR molecules on their biosynthetic route, after the MHC class II invariant chain is released from the DR heterodimer. gB-DR complexes were detected in a post-Golgi compartment and in exosomes, but not on the cell surface. Interestingly, increasing expression of gB strongly elevated the amount of DR and CD63 released into the exosome pathway. In conclusion, this is a previously undescribed mode of viral immune evasion involving hijacking of DR from its normal transport route to the cell surface, followed by viral-mediated release of DR into the exosome pathway.

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“…Although ubiquitination of the cytoplasmic region of HLA-DR (DR) regulates its subcellular trafficking, we and others have shown that it is dispensable for exosome entry (15)(16)(17)(18). Interestingly, the nonclassical MHC II molecule HLA-DM (DM) appears to be excluded from exosomes (19,20).…”

mentioning

confidence: 99%

Cutting Edge: HLA-DO Impairs the Incorporation of HLA-DM into Exosomes

Xiu

Côté

Bourgeois-Daigneault

et al. 2011

The Journal of Immunology

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In multivesicular bodies, HLA-DM (DM) assists the loading of antigenic peptides on classical MHC class II molecules such as HLA-DR. In cells expressing HLA-DO (DO), DM is redistributed from the internal vesicles to the limiting membrane of these organelles. This suggests that DO might reduce DM incorporation into exosomes, which are shed upon fusion of multivesicular bodies with the plasma membrane. To test this hypothesis, we used the 721.45 B lymphoblastoid cell line and different HeLa cell transfectants. We demonstrate that the poor recovery of DM in exosomes as compared with HLA-DR is not the mere reflection of differences in protein expression. Indeed, we found that DO contributes to the inefficient transfer of DM to exosomes. This negative regulation requires an intact di-leucine endosomal sorting motif in the cytoplasmic tail of HLA-DOβ. These results demonstrate that canonical sorting signals and protein–protein interactions modulate the selection of MHC protein cargos.

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Sorting of MHC Class II Molecules into Exosomes through a Ubiquitin‐Independent Pathway

Abstract: These authors contributed equally to this work.

Cited by 66 publications

References 90 publications

Post-translational add-ons mark the path in exosomal protein sorting

Post-translational add-ons mark the path in exosomal protein sorting

The Herpes Simplex Virus-1 Encoded Glycoprotein B Diverts HLA-DR into the Exosome Pathway

Cutting Edge: HLA-DO Impairs the Incorporation of HLA-DM into Exosomes

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