DOI: 10.1126/science.286.5447.2162. Impaired Immunoproteasome Assembly and Immune Responses in <i> PA28 <sup>−/−</sup> </i> Mice

Impaired Immunoproteasome Assembly and Immune Responses in PA28 −/− Mice

10.1126/science.286.5447.2162

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

In vitro PA28 binds and activates proteasomes . It is shown here that mice with a disrupted PA28b gene lack PA28a and PA28b polypeptides, demonstrating that PA28 functions as a hetero-oligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens is altered in PA28 –/– mice. Cytotoxic T lymphocyte responses are impaired, and assembly of immunoproteasomes is greatly inhibited in mice lacking PA28. These results show that PA28 is necessary for immunoproteasome assembly and is required for efficient antigen processing, thus demonstrating the importance of PA28-mediated proteasome function in immune responses.

Bibliography

Preckel, T., Fung-Leung, W.-P., Cai, Z., Vitiello, A., Salter-Cid, L., Winqvist, O., Wolfe, T. G., Herrath, M. V., Angulo, A., Ghazal, P., Lee, J.-D., Fourie, A. M., Wu, Y., Pang, J., Ngo, K., Peterson, P. A., FruÌh, K., & Yang, Y. (1999). Impaired Immunoproteasome Assembly and Immune Responses in PA28 â/â Mice. Science, 286(5447), 2162â2165.

Authors 18

Tobias Preckel (first)
Wai-Ping Fung-Leung (additional)
Zeling Cai (additional)
Antonella Vitiello (additional)
Luisa Salter-Cid (additional)
Ola Winqvist (additional)
Tom G. Wolfe (additional)
Matthias Von Herrath (additional)
Ana Angulo (additional)
Peter Ghazal (additional)
Jiing-Dwan Lee (additional)
Anne M. Fourie (additional)
Ying Wu (additional)
Jesse Pang (additional)
Karen Ngo (additional)
Per A. Peterson (additional)
Klaus Früh (additional)
Young Yang (additional)

References 31 Referenced 143

10.1146/annurev.immunol.17.1.739
10.1016/S0952-7915(99)80014-4
10.1074/jbc.272.41.25483
10.1074/jbc.272.44.27994
10.1074/jbc.271.30.18237
10.1074/jbc.270.46.27687
10.1016/S0092-8674(00)80097-5
10.1038/381166a0
10.1007/s002510050476
Supplemental Web figures are available at www.sciencemag.org/feature/data/1043186.shl.
10.1038/37670
10.1073/pnas.89.24.12117
Splenocytes were metabolically labeled for 60 min followed by a 60-min chase. NP-40 cell lysates were incubated at 31° 37° and 43°C for 45 min before being subjected to immunoprecipitation with anti-K b or D b . The amounts of class I molecules were quantified. It was found that while an equivalent amount of class I molecules was present in wild-type and PA28 −/− splenocytes before temperature challenge the amount of class I molecules in PA28 −/− cells after the temperature challenge decreased to ∼80% of the wild-type levels.
10.1016/S1074-7613(00)80447-1
. Ovalbumin-loaded LPS blasts from wild-type and PA28 −/− mice were stained with 25D1.16 and analyzed by flow cytometry. It was found that ∼13% of the wild-type cells stained positive whereas no staining of PA28 −/− cells was observed.
10.1084/jem.177.6.1541
T. Preckel and Y. Yang unpublished results.
M. Ho Cytomegalovirus: Biology and Infection (Plenum New York ed. 2 1991).
P. Borrow and M. B. A. Oldstone in Viral Pathogenesis N. Nathanson Ed. (Lippincott-Raven Philadelphia 1997) pp. 593-627
M. J. Buchmeier and A. J. Zajac in Persistent Virus Infections R. Ahmed and I. Chen Eds. (Wiley New York 1999) pp. 575-605.
10.1084/jem.186.2.209
10.1074/jbc.270.40.23808
10.1006/abbi.1998.1037
10.1016/S0092-8674(00)80942-3
Antisera specific to the proteasome subunit C9 LMP2 PA28a and PA28b have been described (3). Antibodies specific to CD4 CD8 CD3-e TCR-ab CD23 CD25 CD28 CD45 CD69 class I and class II molecules were purchased from PharMingen (San Diego CA). 25D1.16 (10) and a PA28a-specific antiserum (2) were kindly provided by A. Porgador and M. Rechsteiner respectively. Metabolic labeling immunoprecipitation immunoblotting and sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) were performed as described (3).
Flad T., et al., Cancer Res. 58, 5803 (1998). / Cancer Res. by Flad T. (1998)
10.1016/S0092-8674(88)91043-4
10.1002/eji.1830270315
10.1038/334156a0
10.1111/1523-1747.ep12340431
All animal experiments were conducted in accordance with institutional guidelines. We thank S. Sutton J. Culver and S. Courtney for technical assistance and J.-F. Huang and G. Schoenhals for critical reading. The technical assistance of the DNA vivarium and peptide synthesis facilities of the R. W. Johnson Pharmaceutical Research Institute is gratefully acknowledged.

Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 5:49 a.m.)
Deposited	1 year, 7 months ago (Jan. 13, 2024, 5:33 a.m.)
Indexed	1 month, 2 weeks ago (July 14, 2025, 11:21 p.m.)
Issued	25 years, 8 months ago (Dec. 10, 1999)
Published	25 years, 8 months ago (Dec. 10, 1999)
Published Print	25 years, 8 months ago (Dec. 10, 1999)

Funders 0

None

BibTeX

@article{Preckel_1999, title={Impaired Immunoproteasome Assembly and Immune Responses in PA28 −/− Mice}, volume={286}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.286.5447.2162}, DOI={10.1126/science.286.5447.2162}, number={5447}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Preckel, Tobias and Fung-Leung, Wai-Ping and Cai, Zeling and Vitiello, Antonella and Salter-Cid, Luisa and Winqvist, Ola and Wolfe, Tom G. and Herrath, Matthias Von and Angulo, Ana and Ghazal, Peter and Lee, Jiing-Dwan and Fourie, Anne M. and Wu, Ying and Pang, Jesse and Ngo, Karen and Peterson, Per A. and Früh, Klaus and Yang, Young}, year={1999}, month=dec, pages={2162–2165} }

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