Role of Furin in Delivery of a CTL Epitope of an Anthrax Toxin‐Fusion Protein

Zhang, Ye; Kida, Yutaka; Kuwano, Koichi; Misumi, Yoshio; Ikehara, Yukio; Arai, Sumio

doi:10.1111/j.1348-0421.2001.tb01279.x

Cited by 15 publications

(10 citation statements)

References 29 publications

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“…This indicates that the cell lines do not differ in the endocytic recycling and processing of surface MHC I. Stryhn et al (26) proposed that suboptimally loaded MHC I exchanges low affinity peptide ligands after reaching the late compartments of the exocytic route. Proprotein convertases (pPCs), which cycle between trans-Golgi network (TGN), plasma membrane and endosomes (9) have been reported to be involved in the generation of peptide Ags for MHC I (10,27). To test whether the high level of surface MHC I expression in cell line T2 (1-2⌬N) depends on the activity of pPCs, we performed surface MHC I-recovery experiments in the presence of increasing (43) and incubated for 1 h at 4°or 37°C.…”

Section: Comparison Of Mhc Class I Processing In Cells Expressing Tapmentioning

confidence: 99%

Critical Role for the Tapasin-Docking Site of TAP2 in the Functional Integrity of the MHC Class I-Peptide-Loading Complex

Leonhardt

Keusekotten

Bekpen

et al. 2005

The Journal of Immunology

103

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The transporter associated with Ag processing (TAP) translocates antigenic peptides into the endoplasmic reticulum for binding onto MHC class I (MHC I) molecules. Tapasin organizes a peptide-loading complex (PLC) by recruiting MHC I and accessory chaperones to the N-terminal regions (N domains) of the TAP subunits TAP1 and TAP2. To investigate the function of the tapasin-docking sites of TAP in MHC I processing, we expressed N-terminally truncated variants of TAP1 and TAP2 in combination with wild-type chains, as fusion proteins or as single subunits. Strikingly, TAP variants lacking the N domain in TAP2, but not in TAP1, build PLCs that fail to generate stable MHC I-peptide complexes. This correlates with a substantially reduced recruitment of accessory chaperones into the PLC demonstrating their important role in the quality control of MHC I loading. However, stable surface expression of MHC I can be rescued in post-endoplasmic reticulum compartments by a proprotein convertase-dependent mechanism.

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Section: Comparison Of Mhc Class I Processing In Cells Expressing Tapmentioning

confidence: 99%

Critical Role for the Tapasin-Docking Site of TAP2 in the Functional Integrity of the MHC Class I-Peptide-Loading Complex

Leonhardt

Keusekotten

Bekpen

et al. 2005

The Journal of Immunology

103

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“…Alternative pathways seem to have a limited contribution, although they generate some of these ligands (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The proteasome is a complex protease located in the cytosol and nucleus.…”

mentioning

confidence: 99%

The Origin of Proteasome-inhibitor Resistant HLA Class I Peptidomes: a Study With HLA-A*68:01

García-Medel

Sanz-Bravo

Barnea

et al. 2012

Molecular & Cellular Proteomics

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Some HLA class I molecules bind a significant fraction of their constitutive peptidomes in the presence of proteasome inhibitors. In this study, A*68:01-bound peptides, and their parental proteins, were characterized through massive mass spectrometry sequencing to refine its binding motif, including the nearly exclusive preference for C-terminal basic residues. Stable isotope tagging was used to distinguish proteasome-inhibitor sensitive and resistant ligands. The latter accounted for less than 20% of the peptidome and, like in HLA-B27, arose predominantly from small and basic proteins. Under the conditions used for proteasome inhibition in vivo, epoxomicin and MG-132 incompletely inhibited the hydrolysis of fluorogenic substrates specific for the tryptic or for both the tryptic and chymotryptic subspecificities, respectively. This incomplete inhibition was also reflected in the cleavage of synthetic peptide precursors of A*68:01 ligands. For these substrates, the inhibition of the proteasome resulted in altered cleavage patterns. However these alterations did not upset the balance between cleavage at peptide bonds resulting in epitope destruction and those leading to their generation. The results indicate that inhibitor-resistant HLA class I ligands are not necessarily produced by non-proteasomal pathways. However, their generation is not simply explained by decreased epitope destruction upon incomplete proteasomal inhibition and may require additional proteolytic steps acting on incompletely processed proteasomal products. Molecular &

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“…In dendritic cells, the lysosomal enzyme cathepsin S was shown to generate a TAP-independent class I ligand for cross-presentation in vivo (31). Furine, a protease of the Golgi, can also generate class I ligands (32)(33)(34). This enzyme, or closely related proprotein convertases, may also provide suitable class I ligands upon failure of quality control mechanisms for peptide loading in the ER (35), although the actual contribution of this enzyme to the constitutive MHC class I-bound peptide repertoires in cells with an intact processing-loading pathway has not yet been confirmed.…”

mentioning

confidence: 99%

Proteasome-independent HLA-B27 Ligands Arise Mainly from Small Basic Proteins

Marcilla

Cragnolini

Castro

2007

Molecular & Cellular Proteomics

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Many of the constitutive peptide ligands of HLA-B27, a molecule strongly associated with spondyloarthritis, are proteasome-independent. Stable isotope tagging, mass spectrometry, and epoxomicin-mediated inhibition were used to determine their percentage, structural features, and parental proteins. Of 104 molecular species examined, 29.8% were proteasome-independent, paralleling the level of HLA-B27 re-expression in the presence of epoxomicin after acid stripping. Proteasome-dependent and -independent ligands differed little in peptide motifs, flanking sequences, and cellular localization of the parental proteins. In contrast, whereas the former set arose from proteins whose size and isoelectric point distribution largely reflected those in the human proteome, proteasome-independent ligands, other than a few matching signal sequences, were almost totally derived from small (about 6 -16.5 kDa) and basic proteins, which account for only 6.6% of the human proteome. Thus, a non-proteasomal proteolytic pathway with strong preference for small proteins is responsible for a significant fraction of the HLA-B27-bound peptide repertoire. Molecular & Cellular Proteomics 6:923-938, 2007.

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Role of Furin in Delivery of a CTL Epitope of an Anthrax Toxin‐Fusion Protein

Cited by 15 publications

References 29 publications

Critical Role for the Tapasin-Docking Site of TAP2 in the Functional Integrity of the MHC Class I-Peptide-Loading Complex

Critical Role for the Tapasin-Docking Site of TAP2 in the Functional Integrity of the MHC Class I-Peptide-Loading Complex

The Origin of Proteasome-inhibitor Resistant HLA Class I Peptidomes: a Study With HLA-A*68:01

Proteasome-independent HLA-B27 Ligands Arise Mainly from Small Basic Proteins

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