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A role for the proteasome regulator PA28α in antigen presentation

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1996

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Soza, Andrea
Eggers, Maren
Kuehn, Lothar
Dick, Tobias P.
Schild, Hansjörg
Rammensee, Hans-Georg
Koszinowski, Ulrich H.
Kloetzel, Peter-M.

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London :

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Published

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Nature. 1996, 381(6578), pp. 166-168. ISSN 0028-0836. Available under: doi: 10.1038/381166a0

Zusammenfassung

Cytotoxic T cells recognize viral proteins as peptide fragments which are produced in the cytosol and transported on major histocompatibility complex (MHC) class I proteins to the cell surface1. Viral peptides that meet the stringent binding characteristics of class I proteins are generated by the 20S proteasome2,3. The interferon (IFN)-γ-inducible activator of the 20S proteasome, PA28 (refs 4–6), strongly influences the proteasomal cleavage pattern in vitro 7. This led us to investigate whether changes in cellular levels of PA28 affect the efficiency of viral antigen processing. A mouse fibroblast line expressing the murine cytomegalovirus pp89 protein was transfected with either the human or murine gene encoding the PA28α subunit, which is sufficient to activate the peptide-hydrolysing activity of the 20S proteasome in vitro. Here we report that enhanced expression of PA28α at a level similar to that obtained after IFN-γ induction resulted in a marked enhancement of recognition by pp89-specific cytotoxic T cells; the presentation of influenza nucleoprotein was also significantly improved. These results demonstrate a fundamental in vivo function for PA28α in antigen processing.

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570 Biowissenschaften, Biologie

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ISO 690GRÖTTRUP, Marcus, Andrea SOZA, Maren EGGERS, Lothar KUEHN, Tobias P. DICK, Hansjörg SCHILD, Hans-Georg RAMMENSEE, Ulrich H. KOSZINOWSKI, Peter-M. KLOETZEL, 1996. A role for the proteasome regulator PA28α in antigen presentation. London :. In: Nature. 1996, 381(6578), pp. 166-168. ISSN 0028-0836. Available under: doi: 10.1038/381166a0
BibTex
@article{Grottrup1996-05-09prote-16677,
  year={1996},
  doi={10.1038/381166a0},
  title={A role for the proteasome regulator PA28α in antigen presentation},
  number={6578},
  volume={381},
  issn={0028-0836},
  journal={Nature},
  pages={166--168},
  author={Gröttrup, Marcus and Soza, Andrea and Eggers, Maren and Kuehn, Lothar and Dick, Tobias P. and Schild, Hansjörg and Rammensee, Hans-Georg and Koszinowski, Ulrich H. and Kloetzel, Peter-M.}
}
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    <dcterms:abstract xml:lang="eng">Cytotoxic T cells recognize viral proteins as peptide fragments which are produced in the cytosol and transported on major histocompatibility complex (MHC) class I proteins to the cell surface1. Viral peptides that meet the stringent binding characteristics of class I proteins are generated by the 20S proteasome2,3. The interferon (IFN)-γ-inducible activator of the 20S proteasome, PA28 (refs 4–6), strongly influences the proteasomal cleavage pattern in vitro 7. This led us to investigate whether changes in cellular levels of PA28 affect the efficiency of viral antigen processing. A mouse fibroblast line expressing the murine cytomegalovirus pp89 protein was transfected with either the human or murine gene encoding the PA28α subunit, which is sufficient to activate the peptide-hydrolysing activity of the 20S proteasome in vitro. Here we report that enhanced expression of PA28α at a level similar to that obtained after IFN-γ induction resulted in a marked enhancement of recognition by pp89-specific cytotoxic T cells; the presentation of influenza nucleoprotein was also significantly improved. These results demonstrate a fundamental in vivo function for PA28α in antigen processing.</dcterms:abstract>
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