A role for the proteasome regulator PA28α in antigen presentation

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

doi:10.1038/381166a0

A role for the proteasome regulator PA28α in antigen presentation

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

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 proteasome^2,3. The interferon (IFN)-γ-inducible activator of the 20S proteasome, PA28 (refs 4-6), strongly influences the proteasomal cleavage pattern in vitro⁷. 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 PA28a 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.

Original language	English
Pages (from-to)	166-168
Number of pages	3
Journal	Nature
Volume	381
Issue number	6578
DOIs	https://doi.org/10.1038/381166a0
State	Published - 1996
Externally published	Yes

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title = "A role for the proteasome regulator PA28α in antigen presentation",

abstract = "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 vitro7. 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 PA28a 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.",

author = "Marcus Groettrup and Andrea Soza and Maren Eggers and Lothar Kuehn and Dick, {Tobias P.} and Hansj{\"o}rg Schild and Rammensee, {Hans Georg} and Koszinowski, {Ulrich H.} and Kloetzel, {Peter M.}",

year = "1996",

month = may,

day = "9",

doi = "10.1038/381166a0",

language = "English",

volume = "381",

pages = "166--168",

journal = "Nature",

issn = "0028-0836",

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T1 - A role for the proteasome regulator PA28α in antigen presentation

AU - Groettrup, Marcus

AU - Soza, Andrea

AU - Eggers, Maren

AU - Kuehn, Lothar

AU - Dick, Tobias P.

AU - Schild, Hansjörg

AU - Rammensee, Hans Georg

AU - Koszinowski, Ulrich H.

AU - Kloetzel, Peter M.

PY - 1996/5/9

Y1 - 1996/5/9

N2 - 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 vitro7. 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 PA28a 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.

AB - 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 vitro7. 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 PA28a 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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DO - 10.1038/381166a0

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AN - SCOPUS:0029918289

SN - 0028-0836

VL - 381

SP - 166

EP - 168

JO - Nature

JF - Nature

IS - 6578

ER -

A role for the proteasome regulator PA28α in antigen presentation

Abstract

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