Crossref journal-article
Rockefeller University Press
The Journal of Experimental Medicine (291)
Abstract

We have analyzed the presentation of human histocompatability leukocyte antigen-A*0201–associated tumor peptide antigen MAGE-3271–279 by melanoma cells. We show that specific cytotoxic T lymphocyte (CTL)-recognizing cells transfected with a minigene encoding the preprocessed fragment MAGE-3271–279 failed to recognize cells expressing the full length MAGE-3 protein. Digestion of synthetic peptides extended at the NH2 or COOH terminus of MAGE-3271–279 with purified human proteasome revealed that the generation of the COOH terminus of the antigenic peptide was impaired. Surprisingly, addition of lactacystin to purified proteasome, though partially inhibitory, resulted in the generation of the antigenic peptide. Furthermore, treatment of melanoma cells expressing the MAGE-3 protein with lactacystin resulted in efficient lysis by MAGE-3271–279–specific CTL. We therefore postulate that the generation of antigenic peptides by the proteasome in cells can be modulated by the selective inhibition of certain of its enzymatic activities.

Bibliography

Valmori, D., Gileadi, U., Servis, C., Dunbar, P. R., Cerottini, J.-C., Romero, P., Cerundolo, V., & Lévy, F. (1999). Modulation of Proteasomal Activity Required for the Generation of a Cytotoxic T Lymphocyte–defined Peptide Derived from the Tumor Antigen MAGE-3. The Journal of Experimental Medicine, 189(6), 895–906.

Authors 8
  1. Danila Valmori (first)
  2. Uzi Gileadi (additional)
  3. Catherine Servis (additional)
  4. P. Rod Dunbar (additional)
  5. Jean-Charles Cerottini (additional)
  6. Pedro Romero (additional)
  7. Vincenzo Cerundolo (additional)
  8. Frédéric Lévy (additional)
References 40 Referenced 98
  1. 10.1016/S0952-7915(98)80040-X / Curr Opin Immunol / Intracellular distribution of proteasomes by Rivett (1998)
  2. 10.1016/S0092-8674(00)80929-0 / Cell / The proteasome: paradigm of a self-compartmentalized protease by Baumeister (1998)
  3. 10.1146/annurev.bi.65.070196.004101 / Annu Rev Biochem / Structure and functions of the 20S and 26S proteasomes by Coux (1996)
  4. 10.1016/S0021-9258(17)41897-7 / J Biol Chem / Identification, purification and characterization of a high molecular weight, ATP-dependent activator (PA700) of the 20S proteasome by Ping (1994)
  5. 10.1016/S0021-9258(19)50047-3 / J Biol Chem / Identification, purification and characterization of a protein activator (PA28) of the 20S proteasome (macropain) by Ping (1992)
  6. 10.1016/S0021-9258(18)41681-X / J Biol Chem / Purification of an 11S regulator of the multicatalytic protease by Dubiel (1992)
  7. 10.1016/S0092-8674(00)80097-5 / Cell / Coordinated dual cleavages induced by the proteasome regulator PA28 lead to dominant MHC ligands by Dick (1996)
  8. 10.1038/386463a0 / Nature / Structure of 20S proteasome from yeast at 2.4 Å resolution by Groll (1997)
  9. 10.1073/pnas.94.7.2939 / Proc Natl Acad Sci USA / Subunit arrangement in the human 20S proteasome by Kopp (1997)
  10. 10.1021/bi00057a022 / Biochemistry / Evidence for the presence of five distinct proteolytic components in the pituitary multicatalytic proteinase complex. Properties of two components cleaving bonds on the carboxyl side of branched chain and small neutral amino acids by Orlowski (1993)
  11. 10.1093/intimm/8.4.467 / Int Immunol / Proteasomes generate in vitro a natural peptide of influenza-A nucleoprotein functional in HLA–B27 antigen assembly by Svensson (1996)
  12. 10.1016/0167-5699(96)10051-7 / Immunol Today / Peptide antigen production by the proteasome: complexity provides efficiency by Groettrup (1996)
  13. 10.1016/S0092-8674(94)90462-6 / Cell / Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules by Rock (1994)
  14. 10.1146/annurev.immunol.16.1.323 / Annu Rev Immunol / Mechanisms of MHC class I–restricted antigen processing by Pamer (1998)
  15. 10.1007/BF02199806 / Immunogenetics / A peptide encoded by the human MAGE3 gene and presented by HLA–B44 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE3. by Herman (1996)
  16. 10.1084/jem.179.3.921 / J Exp Med / Human gene MAGE-3codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes by Gaugler (1994)
  17. 10.1002/eji.1830241218 / Eur J Immunol / A peptide encoded by human gene MAGE-3and presented by HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3 by van der Bruggen (1994)
  18. {'key': '2023072508395133600_B18', 'first-page': '735', 'article-title': 'Analysis of MAGE-3–specific cytolytic T lymphocytes in human leukocytes antigen–A2 melanoma patients', 'volume': '57', 'author': 'Valmori', 'year': '1997', 'journal-title': 'Cancer Res'} / Cancer Res / Analysis of MAGE-3–specific cytolytic T lymphocytes in human leukocytes antigen–A2 melanoma patients by Valmori (1997)
  19. 10.1016/S0960-9822(98)70161-7 / Curr Biol / Direct isolation, phenotyping and cloning of low-frequency antigen-specific cytotoxic T lymphocytes from peripheral blood by Dunbar (1998)
  20. 10.1073/pnas.93.10.4907 / Proc Natl Acad Sci USA / Using ubiquitin to follow the metabolic fate of a protein by Lévy (1996)
  21. {'key': '2023072508395133600_B21', 'first-page': '2236', 'article-title': 'Identification and intracellular location of MAGE-3 gene product', 'volume': '55', 'author': 'Kocher', 'year': '1995', 'journal-title': 'Cancer Res'} / Cancer Res / Identification and intracellular location of MAGE-3 gene product by Kocher (1995)
  22. 10.1016/0022-1759(86)90322-4 / J Immunol Methods / A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes by Espevik (1986)
  23. 10.1016/0022-1759(89)90397-9 / J Immunol Methods / Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill by Hansen (1989)
  24. 10.1111/j.1432-1033.1996.00404.x / Eur J Biochem / Effects of major-histocompatibility-complex-encoded subunits on the peptidase and proteolytic activities of human 20S proteasomes by Ehring (1996)
  25. 10.1016/0198-8859(84)90047-8 / Human Immunol / Homozygous deletions that simultaneously eliminate expressions of class I and class II antigens of EBV-transformed B-lymphoblastoid cells. I. Reduced proliferative responses of autologous and allogeneic T cells to mutant cells that have decreased expression of class II antigens by DeMars (1984)
  26. 10.1002/eji.1830250238 / Eur J Immunol / Genes encoded in the major histocompatibility complex affecting the generation of peptides for TAP transport by Cerundolo (1995)
  27. 10.1016/S0968-0004(97)01122-5 / Trends Biochem Sci / The ubiquitin system by Varshavsky (1997)
  28. 10.4049/jimmunol.159.2.554 / J Immunol / The generation of MHC class I-associated peptides is only partially inhibited by proteasome inhibitors by Vinitsky (1997)
  29. 10.1126/science.7732382 / Science / Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin by Fenteany (1995)
  30. 10.1073/pnas.93.16.8572 / Proc Natl Acad Sci USA / The proteolytic fragments generated by vertebrate proteasomes: structural relationships to major histocompatibility complex class I binding peptides by Niedermann (1996)
  31. 10.1073/pnas.94.20.10850 / Proc Natl Acad Sci USA / Two distinct proteolytic processes in the generation of a major histocompatibility complex class I-presented peptide by Craiu (1997)
  32. 10.4049/jimmunol.159.12.5769 / J Immunol / Selective involvement of proteasomes and cysteine proteases in MHC class I antigen presentation by Lopez (1997)
  33. 10.1038/33443 / Nature / A proteolytic system that compensates for loss of proteasome function by Glas (1998)
  34. 10.1074/jbc.273.40.25637 / J Biol Chem / Contribution of proteasomal β-subunits to the cleavage of peptide substrates analyzed with yeast mutants by Dick (1998)
  35. {'key': '2023072508395133600_B35', 'first-page': '471', 'article-title': 'Probing the specificity of the bovine pituitary multicatalytic proteinase complex by inhibitors, activators, and by chemical modification', 'volume': '50', 'author': 'Wilk', 'year': '1991', 'journal-title': 'Biomed Biochim Acta'} / Biomed Biochim Acta / Probing the specificity of the bovine pituitary multicatalytic proteinase complex by inhibitors, activators, and by chemical modification by Wilk (1991)
  36. 10.4049/jimmunol.158.6.2535 / J Immunol / MHC class I-associated peptides produced from endogenous gene products with vastly different efficiencies by Anton (1997)
  37. 10.4049/jimmunol.156.2.683 / J Immunol / Two Listeria monocytogenes CTL epitopes are processed from the same antigen with different efficiencies by Sijts (1996)
  38. 10.4049/jimmunol.160.10.4859 / J Immunol / Dissociation of proteasomal degradation of biosynthesized viral proteins from generation of MHC class I-associated antigenic peptides by Anton (1998)
  39. 10.4049/jimmunol.158.4.1727 / J Immunol / Regulation of class I-restricted epitope processing by local or distal flanking sequence by Yellen-Shaw (1997)
  40. 10.1073/pnas.95.22.13120 / Proc Natl Acad Sci USA / An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses by André (1998)
Dates
Type When
Created 23 years, 1 month ago (July 26, 2002, 12:48 p.m.)
Deposited 2 years, 1 month ago (July 25, 2023, 5:51 a.m.)
Indexed 3 months, 1 week ago (May 23, 2025, 4:26 a.m.)
Issued 26 years, 5 months ago (March 15, 1999)
Published 26 years, 5 months ago (March 15, 1999)
Published Online 26 years, 5 months ago (March 15, 1999)
Published Print 26 years, 5 months ago (March 15, 1999)
Funders 0

None

@article{Valmori_1999, title={Modulation of Proteasomal Activity Required for the Generation of a Cytotoxic T Lymphocyte–defined Peptide Derived from the Tumor Antigen MAGE-3}, volume={189}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.189.6.895}, DOI={10.1084/jem.189.6.895}, number={6}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Valmori, Danila and Gileadi, Uzi and Servis, Catherine and Dunbar, P. Rod and Cerottini, Jean-Charles and Romero, Pedro and Cerundolo, Vincenzo and Lévy, Frédéric}, year={1999}, month=mar, pages={895–906} }