The major substrates for TAP in vivo are derived from newly synthesized proteins

Reits, Eric; Vos, J. Chris; Grommé, Monique; Neefjes, Jacques

doi:10.1038/35008103

Cited by 368 publications

(310 citation statements)

References 28 publications

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“…Changes in the fraction of TAP-associated HLA-A2 molecules were measured biochemically and in terms of changes in lateral diffusion in the ER membrane using FRAP. D measured for A2-YFP in HeLa cells was comparable with that reported for A2-GFP in Mel JuSo cells (26). However, whereas adding peptide increased D of the mouse MHC class I molecule, H2L d -GFP, in L cells (17), it had no detectable effect on D of HLA-A2 in HeLa cells.…”

Section: Discussionsupporting

confidence: 81%

Clustering of Peptide-Loaded MHC Class I Molecules for Endoplasmic Reticulum Export Imaged by Fluorescence Resonance Energy Transfer

Pentcheva

Edidin

2001

The Journal of Immunology

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Fluorescence resonance energy transfer between cyan fluorescent protein- and yellow fluorescent protein-tagged MHC class I molecules reports on their spatial organization during assembly and export from the endoplasmic reticulum (ER). A fraction of MHC class I molecules is clustered in the ER at steady state. Contrary to expectations from biochemical models, this fraction is not bound to the TAP. Instead, it appears that MHC class I molecules cluster after peptide loading. This clustering points toward a novel step involved in the selective export of peptide-loaded MHC class I molecules from the ER. Consistent with this model, we detected clusters of wild-type HLA-A2 molecules and of mutant A2-T134K molecules that cannot bind TAP, but HLA-A2 did not detectably cluster with A2-T134K at steady state. Lactacystin treatment disrupted the HLA-A2 clusters, but had no effect on the A2-T134K clusters. However, when cells were fed peptides with high affinity for HLA-A2, mixed clusters containing both HLA-A2 and A2-T134K were detected.

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Section: Discussionsupporting

confidence: 81%

Clustering of Peptide-Loaded MHC Class I Molecules for Endoplasmic Reticulum Export Imaged by Fluorescence Resonance Energy Transfer

Pentcheva

Edidin

2001

The Journal of Immunology

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“…DRiPs are ubiquitinylated polypeptides that are generated as a result of an inaccurate and/or premature termination of mRNA translation [85][86][87][88] . The recent decoding of the human and mouse genome will allow for the precise assessment of the origin of MHC class I bound peptides, i.e., if they originate from "out of frame" translational products or fully assembled functional proteins in the cell.…”

Section: Classical Mhc Class I and Class Ii Antigen Loading Pathwaysmentioning

confidence: 99%

Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance

Nedjic

Aichinger

Emmerich

et al. 2008

Nature

451

422

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“…In addition to the aforementioned exogenous route of partially proteasome-dependent antigen processing in DCs, MHC-I antigen processing of endogenous proteins from defective ribosomal products (DRiPs) [26,27] is tightly coordinated within DC maturation as well: DRiPs transiently accumulate as polyubiquitinylated conglomerates in DALISs during DC maturation [ 28,29]. To study this process in the murine model of ongoing enterovirus myocarditis, poly-ubiquitinylation and DALIS formation were assessed in DCs from both C57BL/6 and A.BY/SnJ mice.…”

Section: Ubiquitinylation/dalis Accumulation/isgylation In Dcs In Cvbmentioning

confidence: 99%

Antigen‐presentation capacity of dendritic cells is impaired in ongoing enterovirus myocarditis

et al. 2011

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Coxsackievirus B3 (CVB3)‐infection is a frequent cause of acute myocarditis, which may result in chronic myocarditis and virus persistence. Investigation of the initial immune responses to CVB3 may shed light on the mechanisms that contribute to ongoing disease. DCs, as key professional APCs, were investigated in two MHC‐matched hosts: while C57BL/6 mice are resistant to chronic CVB3‐myocarditis, the A.BY/SnJ mouse strain exhibits susceptibility. DC maturation and activation were critically impaired in A.BY/SnJ mice, as reflected by the failure of DCs to induce co‐stimulatory molecules and cytokine/chemokine responses. MHC class I‐restricted antigen presentation via the cross‐presentation pathway was also affected in DCs from A.BY/SnJ mice. DC maturation involves the accumulation of DC aggresome‐like induced structures (DALISs) and the transient storage of defective ribosomal products (DRiPs). DCs from A.BY/SnJ mice showed permanent DALIS accumulation; the detection of poly‐ubiquitinylated CVB3 proteins in these DALISs suggested a limitation in the MHC class I antigenic supply in this host. In conclusion, ongoing chronic disease in A.BY/SnJ mice due to a failure to clear the virus may be attributed to defects in DC maturation/activation and DC MHC class I antigen processing.

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The major substrates for TAP in vivo are derived from newly synthesized proteins

Cited by 368 publications

References 28 publications

Clustering of Peptide-Loaded MHC Class I Molecules for Endoplasmic Reticulum Export Imaged by Fluorescence Resonance Energy Transfer

Clustering of Peptide-Loaded MHC Class I Molecules for Endoplasmic Reticulum Export Imaged by Fluorescence Resonance Energy Transfer

Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance

Antigen‐presentation capacity of dendritic cells is impaired in ongoing enterovirus myocarditis

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