Analysis of the Processing of Seven Human Tumor Antigens by Intermediate Proteasomes
| Autor: | Jacques Chapiro, Vincent Stroobant, Benoît Guillaume, Didier Colau, Marie-Pierre Bousquet-Dubouch, Alexandre Dalet, Nicolas Parmentier, Benoît Van den Eynde |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Proteasome Endopeptidase Complex
Immunology Antigen presentation Epitopes T-Lymphocyte Peptide Biology Epitope MART-1 Antigen Antigen Antigens Neoplasm Cell Line Tumor Humans Immunology and Allergy Amino Acid Sequence Melanoma Peptide sequence chemistry.chemical_classification Antigen Presentation Monophenol Monooxygenase HEK 293 cells Peptide Fragments In vitro Clone Cells Neoplasm Proteins HEK293 Cells Proteasome Biochemistry chemistry Hydrophobic and Hydrophilic Interactions Protein Processing Post-Translational gp100 Melanoma Antigen |
| Zdroj: | The Journal of Immunology. 189:3538-3547 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1103213 |
| Popis: | We recently described two proteasome subtypes that are intermediate between the standard proteasome and the immunoproteasome. They contain only one (β5i) or two (β1i and β5i) of the three inducible catalytic subunits of the immunoproteasome. They are present in tumor cells and abundant in normal human tissues. We described two tumor antigenic peptides that are uniquely produced by these intermediate proteasomes. In this work, we studied the production by intermediate proteasomes of tumor antigenic peptides known to be produced exclusively by the immunoproteasome (MAGE-A3114–122, MAGE-C242–50, MAGE-C2336–344) or the standard proteasome (Melan-A26–35, tyrosinase369–377, gp100209–217). We observed that intermediate proteasomes efficiently produced the former peptides, but not the latter. Two peptides from the first group were equally produced by both intermediate proteasomes, whereas MAGE-C2336–344 was only produced by intermediate proteasome β1i-β5i. Those results explain the recognition of tumor cells devoid of immunoproteasome by CTL recognizing peptides not produced by the standard proteasome. We also describe a third antigenic peptide that is produced exclusively by an intermediate proteasome: peptide MAGE-C2191–200 is produced only by intermediate proteasome β1i-β5i. Analyzing in vitro digests, we observed that the lack of production by a given proteasome usually results from destruction of the antigenic peptide by internal cleavage. Interestingly, we observed that the immunoproteasome and the intermediate proteasomes fail to cleave between hydrophobic residues, despite a higher chymotrypsin-like activity measured on fluorogenic substrates. Altogether, our results indicate that the repertoire of peptides produced by intermediate proteasomes largely matches the repertoire produced by the immunoproteasome, but also contains additional peptides. |
| Databáze: | OpenAIRE |
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