Header

UZH-Logo

Maintenance Infos

Structural plasticity of the proteasome and its function in antigen processing


Groettrup, M; van den Broek, M; Schwarz, K; Macagno, A; Khan, S; de Giuli, R; Schmidtke, G (2001). Structural plasticity of the proteasome and its function in antigen processing. Critical Reviews in Immunology, 21(4):339-358.

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)-gamma and tumor necrosis factor (TNF)-alpha 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-gamma-mediated induction of the proteasome regulator PA28alpha/beta and the downregulation of PA28gamma. 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.

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)-gamma and tumor necrosis factor (TNF)-alpha 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-gamma-mediated induction of the proteasome regulator PA28alpha/beta and the downregulation of PA28gamma. 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.

Statistics

Citations

Dimensions.ai Metrics
36 citations in Web of Science®
42 citations in Scopus®
64 citations in Microsoft Academic
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2001
Deposited On:08 Feb 2018 15:33
Last Modified:19 Feb 2018 22:10
Publisher:Begell House
ISSN:1040-8401
OA Status:Closed
PubMed ID:11922078

Download

Full text not available from this repository.
Get full-text in a library