Alternative pathways for MHC class I presentation: a new function for autophagy

Chemali, Magali; Radtke, Kerstin; Desjardins, Michel; English, Luc

doi:10.1007/s00018-011-0660-3

Cited by 62 publications

(57 citation statements)

References 76 publications

(146 reference statements)

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“…In order to be presented on MHC class I molecules, antigens must be processed to peptides, classically by the proteasome. However, it has recently been shown that antigens can be processed via the lysosome, following autophagy or mitophagy [9,10]. Matheoud et al now show that, in addition, mitochondrial proteins can be transported to the lysosome by MDVs for subsequent presentation on MHC class I molecules.…”

mentioning

confidence: 99%

Presenting mitochondrial antigens: PINK1, Parkin and MDVs steal the show

Roberts

Fon

2016

Cell Res

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confidence: 99%

Presenting mitochondrial antigens: PINK1, Parkin and MDVs steal the show

Roberts

Fon

2016

Cell Res

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“…In contrast to the mostly cytoplasmic and ER production of the MHC class I peptidome, the class II peptidome is produced in a special compartment, associated with the endolysosome pathway (18 -20). This pathway is also thought to participate in the cross presentation of class I peptides, derived from proteins up-taken by professional antigen presenting cells (21), (reviewed in (15)(16)(17)22)). …”

mentioning

confidence: 99%

The Effect of Proteasome Inhibition on the Generation of the Human Leukocyte Antigen (HLA) Peptidome

Milner

Gutter-Kapon

Bassani-Strenberg

et al. 2013

Molecular & Cellular Proteomics

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The Major histocompatibility complex (MHC) class I peptidome is thought to be generated mostly through proteasomal degradation of cellular proteins, a notion that is based on the alterations in presentation of selected peptides following proteasome inhibition. We evaluated the effects of proteasome inhibitors, epoxomicin and bortezomib, on human cultured cancer cells. Because the inhibitors did not reduce the level of presentation of the cell surface human leukocyte antigen (HLA) molecules, we followed their effects on the rates of synthesis of both HLA peptidome and proteome of the cells, using dynamic stable isotope labeling in tissue culture (dynamic-SILAC). The inhibitors reduced the rates of synthesis of most cellular proteins and HLA peptides, yet the synthesis rates of some of the proteins and HLA peptides was not decreased by the inhibitors and of some even increased. Therefore, we concluded that the inhibitors affected the production of the HLA peptidome in a complex manner, including modulation of the synthesis rates of the source proteins of the HLA peptides, in addition to their effect on their degradation. The collected data may suggest that the current reliance on proteasome inhibition may overestimate the centrality of the proteasome in the generation of the MHC peptidome. It is therefore suggested that the relative contribution of the proteasomal and nonproteasomal pathways to the production of the MHC peptidome should be revaluated in accordance with the inhibitors effects on the synthesis rates of the source proteins of the MHC peptides. Molecular & Cellular Proteomics 12:

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“…Interestingly, a recent study showed that, following autophagy, some viral Ags could be processed and directly loaded on MHC I within autophagolysosomal compartments (81). Thus, autophagy appears to be a possible route to take up cytosolic Ags and deliver them to endovacuolar compartments (23). However, our findings suggest a more complex Ag trafficking between endovacuolar compartments and the cytosol.…”

Section: Discussionmentioning

confidence: 56%

“…A variation of this latter pathway has been proposed in which Ags undergo cathepsin-dependent preprocessing in late endosomal compartments before they are transported to the cytosol where they are further processed by the proteasome (22). Thus, it seems that multiple pathways coexist and that they functionally cooperate with each other (23).…”

mentioning

confidence: 99%

Amphisomal Route of MHC Class I Cross-Presentation in Bacteria-Infected Dendritic Cells

Fiegl

Kägebein

Liebler-Tenorio

et al. 2013

The Journal of Immunology

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Dendritic cells (DCs) are among the first professional APCs encountered by the obligate intracellular bacterium Chlamydia during infection. Using an established mouse bone marrow–derived DC line, we show that DCs control chlamydial infection in multiple small inclusions characterized by restricted bacterial growth, impaired cytosolic export of the virulence factor chlamydial protease–like activity factor, and interaction with guanylate-binding protein 1, a host cell factor involved in the initiation of autophagy. During maturation of infected DCs, chlamydial inclusions disintegrate, likely because they lack chlamydial protease–like activity factor–mediated protection. Released cytosolic Chlamydia are taken up by autophagosomes and colocalize with cathepsin-positive amphisomal vacuoles, to which peptide transporter TAP and upregulated MHC class I (MHC I) are recruited. Chlamydial Ags are subsequently generated through routes involving preprocessing in amphisomes via cathepsins and entry into the cytosol for further processing by the proteasome. Finally, bacterial peptides are reimported into the endosomal pathway for loading onto recycling MHC I. Thus, we unravel a novel pathway of MHC I–mediated cross-presentation that is initiated with a host cellular attack physically disrupting the parasitophorous vacuole, involves autophagy to collect cytosolic organisms into autophagosomes, and concludes with complex multistep antigenic processing in separate cellular compartments.

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Alternative pathways for MHC class I presentation: a new function for autophagy

Cited by 62 publications

References 76 publications

Presenting mitochondrial antigens: PINK1, Parkin and MDVs steal the show

Presenting mitochondrial antigens: PINK1, Parkin and MDVs steal the show

The Effect of Proteasome Inhibition on the Generation of the Human Leukocyte Antigen (HLA) Peptidome

Amphisomal Route of MHC Class I Cross-Presentation in Bacteria-Infected Dendritic Cells

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