Biomolecules 2014, 4(4), 994-1025; doi:10.3390/biom4040994
Proteasome Subtypes and Regulators in the Processing of Antigenic Peptides Presented by Class I Molecules of the Major Histocompatibility Complex
1
Ludwig Institute for Cancer Research, Brussels 1200, Belgium
2
WELBIO (Walloon Excellence in Life Sciences and Biotechnology), Brussels 1200, Belgium
3
De Duve Institute, Université catholique de Louvain, Brussels 1200, Belgium
*
Author to whom correspondence should be addressed.
Received: 30 July 2014 / Revised: 2 October 2014 / Accepted: 29 October 2014 / Published: 18 November 2014
(This article belongs to the Special Issue Proteasomes and Its Regulators)
Abstract
The proteasome is responsible for the breakdown of cellular proteins. Proteins targeted for degradation are allowed inside the proteasome particle, where they are cleaved into small peptides and released in the cytosol to be degraded into amino acids. In vertebrates, some of these peptides escape degradation in the cytosol, are loaded onto class I molecules of the major histocompatibility complex (MHC) and displayed at the cell surface for scrutiny by the immune system. The proteasome therefore plays a key role for the immune system: it provides a continued sampling of intracellular proteins, so that CD8-positive T-lymphocytes can kill cells expressing viral or tumoral proteins. Consequently, the repertoire of peptides displayed by MHC class I molecules at the cell surface depends on proteasome activity, which may vary according to the presence of proteasome subtypes and regulators. Besides standard proteasomes, cells may contain immunoproteasomes, intermediate proteasomes and thymoproteasomes. Cells may also contain regulators of proteasome activity, such as the 19S, PA28 and PA200 regulators. Here, we review the effects of these proteasome subtypes and regulators on the production of antigenic peptides. We also discuss an unexpected function of the proteasome discovered through the study of antigenic peptides: its ability to splice peptides. View Full-TextKeywords:
antigenic peptides; proteasome; regulator; peptide splicing; processing; CTL
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Vigneron, N.; Van den Eynde, B.J. Proteasome Subtypes and Regulators in the Processing of Antigenic Peptides Presented by Class I Molecules of the Major Histocompatibility Complex. Biomolecules 2014, 4, 994-1025.
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