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 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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References
Rammensee, H. G., Falk, K. & Rötzschke, O. A. Rev. Immun. 11, 213–244 (1993).
Boes, B. et al. J. exp. Med. 179, 901–909 (1994).
Rock, K. L. et al. Cell 78, 761–771 (1994).
Yukawa, M. et al. Biochem. biophys. Res. Commun. 178, 256–262 (1991).
Chu-Ping, M., Slaughter, C. A. & DeMartino, G. N. J. biol. Chem. 267, 10515–10523 (1992).
Dubiel, W., Pratt, G., Ferrell, K. & Rechsteiner, M. J. biol. Chem. 267, 22369–22377 (1992).
Groettrup, M. et al. J. biol. Chem. 270, 23808–23815 (1995).
Realini, C., Dubiel, W., Pratt, G., Ferrell, K. & Rechsteiner, M. J. biol. Chem. 269, 20727–20732 (1994).
Mott, J. D. et al. J. biol. Chem. 269, 31466–31471 (1994).
Gray, C. W., Slaughter, C. A. & DeMartino, G. N. J. molec. Biol. 236, 7–15 (1994).
Honore, B., Leffers, H., Madsen, P. & Celis, J. E. Eur. J. Biochem. 218, 421–430 (1993).
Ahn, J. Y. et al. FEBS Lett. 366, 37–42 (1995).
Realini, C., Rogers, S. W. & Rechsteiner, M. FEBS Lett. 348, 109–113 (1994).
Del Val, M. et al. J. Virol. 65, 3641–3646 (1991).
Rötzschke, O., Falk, K., Faath, S. & Rammensee, H.-G. J. exp. Med. 174, 1059–1071 (1991).
Del Val, M., Münch, K., Reddehase, M. J. & Koszinowski, U. H. Cell 58, 305–315 (1989).
Seelig, A., Boes, B. & Kloetzel, P. M. Enzyme Protein 47, 330–342 (1993).
Koszinowski, U. H. et al. J. Virol. 58, 59–66 (1986).
Keil, G. M., Fibl, M. R. & Koszinowski, U. H. J. Virol. 54, 422–428 (1985).
Groettrup, M., Baron, A., Griffiths, G., Palacios, R. & von Boehmer, H. EMBO J. 11, 2735–2746 (1992).
Rötzschke, O. et al. Nature 348, 252–254 (1990).
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Groettrup, M., Soza, A., Eggers, M. et al. A role for the proteasome regulator PA28α in antigen presentation. Nature 381, 166–168 (1996). https://doi.org/10.1038/381166a0
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DOI: https://doi.org/10.1038/381166a0
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