Efficiency of MHC class I antigen processing: A quantitative analysis

Villanueva, Merceditas; Fischer, Philip R.; Feen, Kevin; Pamer, Eric G.

doi:10.1016/1074-7613(94)90090-6

Cited by 117 publications

(119 citation statements)

References 39 publications

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“…The situation might be different for the class I-restricted CD8+ response. This is, as with other bacteria such as Listeria, narrowly confined to a few proteins and often to only 1 epitope on each (28). This makes it more likely that CD8+ T cells would recognize a common epitope shared by different bacteria.…”

Section: Bacterial Antigen Persisting In the Joint As The Cause Of Spmentioning

confidence: 95%

“…Differences between patients and healthy controls in the proteasome genes, responsible for protein degradation in the cytoplasm, or the transporterassociated proteins ("TAP") genes, responsible for the transport of peptides through the endoplasmatic reticulum, have not been found to date. However, the possibility of such a difference has not been excluded, and furthermore, other ill-defined mechanisms might lead to qualitatively or quantitatively different epitope presentation (28).…”

Section: Bacterial Antigen Persisting In the Joint As The Cause Of Spmentioning

confidence: 99%

“…This correlates nicely with the downregulation of bacterial membrane proteins and upregulation of the 60-kd heat-shock protein observed during persistent infection of cells with C trachomatis in vitro (41), a situation similar to that in arthritis. It has been shown recently that intracellular protein concentration is correlated directly with antigenicity in Listeria infection, thus emphasizing the importance of the amount of protein expressed, for immunodominance (28).…”

Section: Bacterial Antigen Persisting In the Joint As The Cause Of Spmentioning

confidence: 99%

See 2 more Smart Citations

Pathogenesis of spondylarthropathies

Sieper

Braun

1995

Arthritis & Rheumatism

152

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Section: Bacterial Antigen Persisting In the Joint As The Cause Of Spmentioning

confidence: 95%

Section: Bacterial Antigen Persisting In the Joint As The Cause Of Spmentioning

confidence: 99%

Section: Bacterial Antigen Persisting In the Joint As The Cause Of Spmentioning

confidence: 99%

See 1 more Smart Citation

Pathogenesis of spondylarthropathies

Sieper

Braun

1995

Arthritis & Rheumatism

152

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“…These three peptides are bound by H2-K d MHC class I molecules and are recognized by L. monocytogenes-specific CTL. Following secretion into the host cell cytosol, p60 is degraded with a half-life of approximately 90 min (35). Approximately 3% of degraded p60 molecules are processed into p60 217-225 (35), and approximately 30% are processed into p60 449 -457 (34).…”

mentioning

confidence: 99%

“…Following secretion into the host cell cytosol, p60 is degraded with a half-life of approximately 90 min (35). Approximately 3% of degraded p60 molecules are processed into p60 217-225 (35), and approximately 30% are processed into p60 449 -457 (34). LLO is also rapidly degraded in the host cytosol, and approximately 10 -20% of degraded LLO molecules give rise to LLO 91-99 (36).…”

mentioning

confidence: 99%

The Listeria monocytogenes-secreted p60 Protein Is an N-end Rule Substrate in the Cytosol of Infected Cells

Sijts¹,

Pilip

Pamer

1997

Journal of Biological Chemistry

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Cytosolic antigen degradation is an initial step in the generation of major histocompatibility complex (MHC) class I-associated cytolytic T lymphocyte epitopes. Intracellular Listeria monocytogenes secretes p60, a murein hydrolase, into the host cell cytosol, where it is degraded by proteasomes. Roughly 3% of degraded p60 gives rise to p60 217-225, a nonamer peptide that is bound by H-2K d MHC class I molecules. Herein, we introduce targeted deletions throughout the p60 gene to identify potential proteolytic signals within p60. Degradation of mutant forms of p60 was investigated in macrophages infected with recombinant L. monocytogenes. We found that deletions within the amino-terminal two-thirds of p60 enhanced cytosolic degradation. In contrast, truncation of the C terminus resulted in modest stabilization of p60 in the host cell cytosol. Because a protein's N-terminal amino acid can determine its rate of degradation, we mutagenized this residue in p60 into known stabilizing and destabilizing residues. Valine substitution dramatically stabilized cytosolic p60 molecules, while substitution with aspartic acid resulted in rapid degradation. The number of p60 217-225 epitopes isolated from infected cells directly correlated with the rates of p60 degradation. Our data, therefore, indicate that the N-terminal amino acid and multiple internal regions of p60 influence its stability in the cytosol of infected cells. Antigen degradation and epitope generation are linked, and different degradation signals can channel bacterial proteins into the MHC class I antigen processing pathway.MHC 1 class I molecules bind peptides that are generated in the cytosol by proteasome-mediated degradation of endogenous and foreign proteins (1-3). Proteasomes are multienzyme complexes consisting of a 20 S catalytic core that associates with regulatory subunits to make a 26 S particle. Membrane-permeable proteasome inhibitors prevent the generation of most antigenic peptides and, because of a shortage of peptide, impair MHC class I egress from the endoplasmic reticulum (4 -6). The sites of proteasome cleavage can influence the efficiency of antigen processing into MHC class I-associated peptides (7-9). Two MHC-encoded proteasome subunit proteins, LMP-2 and LMP-7, and the proteasome regulator PA28 modify proteasome specificity and enhance MHC class I antigen processing (10 -14). Peptides generated in the cytosol by proteasomes are translocated into the endoplasmic reticulum by the transporter associated with antigen processing (15) and, if they conform to the appropriate motif, are bound by MHC class I molecules (16). The assembled complexes travel to the cell surface, where they are presented to CD8ϩ cytolytic T lymphocytes (CTL).Cytosolic protein degradation is generally very specific and regulated. Thus, most endogenous proteins contain or acquire degradation signals prior to proteasome-mediated destruction. One of the best characterized mechanisms for marking proteins for cytosolic degradation involves the ubiquitination of target protei...

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Differential processing of influenza nucleoprotein in human and mouse cells

1998

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To investigate how early events in antigen processing affect the repertoire of peptides presented by MHC class I molecules, we compared the presentation of the influenza A nucleoprotein epitope 265-273 by HLA-A3 class I molecules in human and mouse cells. Mouse cells that express HLA-A3 failed to present the NP265-273 peptide when contained within the full-length nucleoprotein, to HLA-A3-restricted human cytotoxic T lymphocytes. However, when the epitope was generated directly in the cytosol using a recombinant vaccinia virus that expressed the nonamer peptide, mouse cells were recognized by HLA-A3-restricted CTL. Poor transport of the peptide by mouse TAP was not responsible for the defect as co-infection of mouse cells with recombinant vaccinia viruses encoding the fulllength nucleoprotein and the human TAP1 and TAP2 peptide transporter complex failed to restore presentation. These results therefore demonstrate a differential processing of the influenza nucleoprotein in mouse and human cells. This polymorphism influences the repertoire of peptides presented by MHC class I molecules at the cell surface.

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Efficiency of MHC class I antigen processing: A quantitative analysis

Cited by 117 publications

References 39 publications

Pathogenesis of spondylarthropathies

Pathogenesis of spondylarthropathies

The Listeria monocytogenes-secreted p60 Protein Is an N-end Rule Substrate in the Cytosol of Infected Cells

Differential processing of influenza nucleoprotein in human and mouse cells

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