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Critical Reviews™ in Immunology

ISSN for PRINT: 1040-8401

Institutional price:	$831.00
Issues per year:	6

Best Paper Award Selection - Editorial Board Site

2001, Volume21

91 pages

Issue price - $132.00

Structural Plasticity of the Proteasome and Its Function in Antigen Processing

Marcus Groettrup
Research Department, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

Maries van den Broek
Institute of Experimental Immunology, Department of Pathology, University Hospital Zurich, Zurich, Switzerland

Katrin Schwarz
Research Department, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

Annalisa Macagno
Research Department, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

Selina Khan
Research Department, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

Rita de Giuli
Research Department, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

Gunter Schmidtke
Research Department, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

ABSTRACT

The proteasome is the main provider of peptide ligands for major histocompatibility complex class I molecules. During an immune response to pathogens, the proinflammatory cytokine interferon (IFN)-g and tumor necrosis factor (TNF)-a are released, which induce the proteasome subunits LMP2, LMP7, and MECL-1. These replace the constitutively expressed active site subunits of the proteasome (delta, MB1, and Z) leading to a marked change in the cleavage preference of the proteasome and the production of T-cell epitopes. Proteasome activity is further changed by the IFN)-g–mediated induction of the proteasome regulator PA28a/b and the downregulation of PA28g. Why such an extensive exchange of proteasome active site subunits and regulators occurs is still poorly understood. In this article we discuss recent insights in the structural consequences of proteasome reorganization and their effects on epitope generation and shaping of the cytotoxic immune response. Moreover, we review the latest data on how the ubiquitin pathway targets protein antigens for peptide processing and discuss the potential of proteasome inhibitors for the modulation of antigen presentation.