Subunit of the '20S' proteasome (multicatalytic proteinase) encoded by the major histocompatibility complex

Abstract

CYTOTOXIC T lymphocytes recognize fragments (peptides) of protein antigens presented by major histocompatibility complex (MHC) class I molecules. In general, the peptides are derived from cytosolic proteins and are then transported to the endoplasmic reticulum where they assemble with the MHC class I heavy chains and β2-microglobulin to form stable and functional class I molecules1–4. The proteases involved in the generation of these peptides are unknown. One candidate is the proteasome, a non-lysosomal proteinase complex abundantly present in the cytosol. Proteasomes have several proteolytically active sites and are complexes of high relative molecular mass (Mr about 600K), consisting of about 20–30 subunits with Mrs between 15 and 30K (refs 5–10). Here we show that at least one of these subunits is encoded by the mouse MHC in the region between the K locus and the MHC class II region, and inducible by interferon-γ. This raises the intriguing possibility that the MHC encodes not only the MHC class I molecules themselves but also proteases involved in the formation of MHC-binding peptides.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Townsend, A. R. M., Gotch, F. M. & Davey, J. Cell 42, 457–467 (1985).

    CAS  Article  Google Scholar 

  2. 2

    Morrison, L. A., Lukacher, A. E., Braciale, B. L., Fan, D. P. & Braciole, T. J. J. exp. Med. 163, 903–921 (1986).

    CAS  Article  Google Scholar 

  3. 3

    Moore, M., Carbone, F. R. & Bevan, M. J. Cell 54, 777–785 (1988).

    CAS  Article  Google Scholar 

  4. 4

    Townsend, A. R. M. et al. Nature 340, 443–448 (1989).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Rivett, J. Archs Biochem. Biophys. 268, 1–8 (1989).

    CAS  Article  Google Scholar 

  6. 6

    Kopp, F., Steiner, R., Dahlmann, B., Kuehn, L. & Reinauer, H. Biochem. biophys. Acta 872, 253–260 (1986).

    CAS  PubMed  Google Scholar 

  7. 7

    Tanaka, K., Ichihara, A., Waxman, L. & Goldberg, A. L. J. biol. Chem. 263, 15197–15203 (1986).

    Google Scholar 

  8. 8

    Kloetzel, P. M. Molec. Biol. Rep. 12, 223–227 (1987).

    Article  Google Scholar 

  9. 9

    Kloetzel, P. M. et al. Biomed. biochim. Acta 50, 4–6; 451–457 (1991).

    CAS  PubMed  Google Scholar 

  10. 10

    Falkenburg, P. E. and Kloetzel, P. M. J. biol. Chem. 264, 6660–6666 (1989).

    CAS  PubMed  Google Scholar 

  11. 11

    Seelig, A., Kloetzel, P. M., Kuehn, L. & Dahlmann, B. Biochem. J. (in the press).

  12. 12

    Haass, Ch., Pesold-Hurt, B., Multhamp, G., Beyreuther, K. & Kloetzel, P. M. Gene 90, 235–241 (1990).

    CAS  Article  Google Scholar 

  13. 13

    DeMars, R. et al. Proc. natn. Acad. Sci. U.S.A. 82, 8183–8187 (1985).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Cerundolo, V. et al. Nature 345, 349–352 (1990)

    Article  Google Scholar 

  15. 15

    Hosken, N. A. & Bevan, M. J. Science 248, 367–370 (1990).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Trowsdale, J. et al. Nature 348, 741–744 (1990).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Spies, Th. et al. Nature 348, 744–747 (1990).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Deverson, E. V. et al. Nature 348, 738–741 (1990).

    ADS  CAS  Article  Google Scholar 

  19. 19

    Monaco, J. J., Cho, S. & Attaya, M. Science 250, 1723–1726 (1991).

    ADS  Article  Google Scholar 

  20. 20

    Spies, Th. & De Mars, R. Nature 351, 323–325 (1991).

    ADS  CAS  Article  Google Scholar 

  21. 21

    Lindahl, P., Leary, P. & Gresser, I. Proc. natn. Acad. Sci. U.S.A. 70, 2785–2789 (1973).

    ADS  CAS  Article  Google Scholar 

  22. 22

    Wallach, D., Fellows, M. & Revel, M. Nature 299, 833–836 (1982).

    ADS  CAS  Article  Google Scholar 

  23. 23

    Klar, D. & Hämmerling, G. J. EMBO J. 8, 475–481 (1989).

    CAS  Article  Google Scholar 

  24. 24

    Monaco, J. J. & McDevitt, H. O. Proc. natn. Acad. Sci. U.S.A. 79, 3001–3005 (1982).

    ADS  CAS  Article  Google Scholar 

  25. 25

    Monaco, J. J. & McDevitt, H. O. Nature 309, 797–799 (1984).

    ADS  CAS  Article  Google Scholar 

  26. 26

    Monaco, J. J. & McDevitt, H. O. Hum. Immun. 15, 416–426 (1986).

    CAS  Article  Google Scholar 

  27. 27

    Parham, P. Nature 348, 674–675 (1990).

    ADS  CAS  Article  Google Scholar 

  28. 28

    Dahlmann, B. et al. Baumeister, W. FEBS Lett. 251, 125–131 (1989).

    CAS  Article  Google Scholar 

  29. 29

    Tanaka, K. et al. J. biol. Chem. 263, 16209–16217 (1988).

    CAS  PubMed  Google Scholar 

  30. 30

    Arrigo, A.-P., Simon, M., Darlix, J.-L. & Spahr, P. F. J. molec. Evol. 25, 141–150 (1987).

    ADS  CAS  Article  Google Scholar 

  31. 31

    Fujiwara, T. et al. J. biol. Chem. 265, 16604–16613 (1990).

    CAS  Google Scholar 

  32. 32

    Uematsu, Y., Fischer-Lindahl, K. & Steinmetz, M. Immunogenetics 27, 96–101 (1988).

    CAS  Article  Google Scholar 

  33. 33

    Koch, N. & Hämmerling, G. J. J. Immun. 128, 1155–1158 (1982).

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ortiz-Navarrete, V., Seelig, A., Gernold, M. et al. Subunit of the '20S' proteasome (multicatalytic proteinase) encoded by the major histocompatibility complex. Nature 353, 662–664 (1991). https://doi.org/10.1038/353662a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.