Selective proteasome inhibitors: modulators of antigen presentation?

The proteasome is the main nonlysosomal endoprotease in the cytoplasm and nucleus of all eukaryotic cells. It is responsible for the generation of most antigenic peptides as ligands for major histocompatibility complex (MHC) class I proteins. The proteasome hence qualifies as a target for modifying...

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Bibliographic Details
Published in:Drug Discovery Today 1999-02, Vol.4 (2), p.63-71
Main Authors: Groettrup, Marcus, Schmidtke, Gunter
Format: Article
Language:English
Subjects:
antigen presentation
Biological and medical sciences
Immunomodulators
lactacystin
Medical sciences
MHC class I
Pharmacology. Drug treatments
Proteasome
proteasome inhibitors
ritonavir
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Summary:The proteasome is the main nonlysosomal endoprotease in the cytoplasm and nucleus of all eukaryotic cells. It is responsible for the generation of most antigenic peptides as ligands for major histocompatibility complex (MHC) class I proteins. The proteasome hence qualifies as a target for modifying or silencing antigen processing and presentation to cytotoxic T cells, which are important players in transplant rejection and autoimmune disease. The authors summarize recent progress in the understanding of antigen processing by the proteasome and discuss the potential of novel and selective proteasome inhibitors as drugs for suppressing or modifying the cytotoxic immune response.
ISSN:1359-6446
1878-5832
DOI:10.1016/S1359-6446(98)01292-6