The ubiquitin-like modifier FAT10 in antigen processing and antimicrobial defense

Michael Basler; Stefanie Buerger; Marcus Groettrup

doi:10.1016/j.molimm.2015.04.012

The ubiquitin-like modifier FAT10 in antigen processing and antimicrobial defense

Mol Immunol. 2015 Dec;68(2 Pt A):129-32. doi: 10.1016/j.molimm.2015.04.012. Epub 2015 May 14.

Authors

Michael Basler¹, Stefanie Buerger², Marcus Groettrup³

Affiliations

¹ Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany; Biotechnology Institute Thurgau (BITg) at the University of Konstanz, CH-8280 Kreuzlingen, Switzerland. Electronic address: Michael.Basler@uni-konstanz.de.
² Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany.
³ Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany; Biotechnology Institute Thurgau (BITg) at the University of Konstanz, CH-8280 Kreuzlingen, Switzerland. Electronic address: Marcus.Groettrup@uni-konstanz.de.

PMID: 25983082
DOI: 10.1016/j.molimm.2015.04.012

Abstract

The ubiquitin-like modifier (ULM) HLA-F adjacent transcript 10 (FAT10) is encoded in the MHC locus, is up-regulated during dendritic cell maturation, is highly expressed in lymphoid tissues, and strongly induced by interferon (IFN)-γ and tumor necrosis factor (TNF)-α. FAT10 is the only ULM known to date which directly targets its hundreds of substrates for degradation by the proteasome. This implies a role for FAT10 in antigen presentation. Indeed, fusion of FAT10 to viral proteins enhanced their presentation along the proteasome dependent MHC class I presentation pathway. In this review we discuss the FAT10 conjugation system as an alternative and distinct pathway for MHC class I and II antigen processing. Furthermore, we review the recent finding that FAT10 plays a role in antimicrobial defense against intracellular pathogens.

Keywords: Antigen presentation; Antigen processing; FAT10; Ubiquitin-like modifier.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antigen Presentation*
Antigens, Bacterial / genetics
Antigens, Bacterial / immunology*
Dendritic Cells / cytology
Dendritic Cells / drug effects
Dendritic Cells / immunology*
Gene Expression Regulation
Histocompatibility Antigens Class I / genetics
Histocompatibility Antigens Class I / immunology
Histocompatibility Antigens Class II / genetics
Histocompatibility Antigens Class II / immunology
Humans
Interferon-gamma / pharmacology
Lymphoid Tissue / cytology
Lymphoid Tissue / drug effects
Lymphoid Tissue / immunology
Proteasome Endopeptidase Complex / immunology
Proteasome Endopeptidase Complex / metabolism
Proteolysis
Signal Transduction
Tumor Necrosis Factor-alpha / pharmacology
Ubiquitination
Ubiquitins / genetics
Ubiquitins / immunology*

Substances

Antigens, Bacterial
Histocompatibility Antigens Class I
Histocompatibility Antigens Class II
Tumor Necrosis Factor-alpha
UBD protein, human
Ubiquitins
Interferon-gamma
Proteasome Endopeptidase Complex