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Nat Immunol. 2004 Jul;5(7):661-9.

Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII.

Author information

  • 1Institut für Biochemie, University Medical School-Charité, Humboldt Universität Monbijoustr.2, 10117 Berlin, Germany. p-m.kloetzel@charite.de

Abstract

The proteasome is key in the cascade of proteolytic processing required for the generation of peptides presented at the cell surface to cytotoxic T lymphocytes by major histocompatibility complex class I molecules. Proteasome-dependent epitope processing is greatly improved through the interferon-gamma-induced formation of immunoproteasomes and the activator complex PA28. Tripeptidyl aminopeptidase II also has a strong effect on epitope generation. With its endoproteolytic and exoproteolytic activities, TPPII acts 'downstream' of the proteasome and relies on products released by the proteasome. The antigen-processing cascade involving different proteolytic systems raises anew the question of how antigenic peptides are generated. We therefore revisit the interferon-gamma-induced immune adaptation of the proteasome and attempt to redefine its function in connection with the emerging importance of TPPII.

PMID:
15224091
DOI:
10.1038/ni1090
[PubMed - indexed for MEDLINE]
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