A role for the proteasome regulator PA28alpha in antigen presentation.

Abstract	Cytotoxic T cells recognize viral proteins as peptide fragments which are produced in the cytosol and transported on major histocompatibility complex (MHC) class I proteins to the cell surface. Viral peptides that meet the stringent binding characteristics of class I proteins are generated by the 20S proteasome. The interferon (IFN)-gamma-inducible activator of the 20S proteasome, PA28, strongly influences the proteasomal cleavage pattern in vitro. This led us to investigate whether changes in cellular levels of PA28 affect the efficiency of viral antigen processing. A mouse fibroblast line expressing the murine cytomegalovirus pp89 protein was transfected with either the human or murine gene encoding the PA28alpha subunit, which is sufficient to activate the peptide-hydrolysing activity of the 20S proteasome in vitro. Here we report that enhanced expression of PA28alpha at a level similar to that obtained after IFN-gamma induction resulted in a marked enhancement of recognition by pp89-specific cytotoxic T cells; the presentation of influenza nucleoprotein was also significantly improved. These results demonstrate a fundamental in vivo function for PA28alpha in antigen processing.
Authors	M Groettrup, A Soza, M Eggers, L Kuehn, T P Dick, H Schild, H G Rammensee, U H Koszinowski, P M Kloetzel
Journal	Nature (Nature) Vol. 381 Issue 6578 Pg. 166-8 (May 09 1996) ISSN: 0028-0836 [Print] England
PMID	8610016 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Autoantigens DNA Primers H-2 Antigens Histocompatibility Antigen H-2D Immediate-Early Proteins Ki antigen Multienzyme Complexes Muscle Proteins PSME1 protein, human Proteins Recombinant Proteins cytomegalovirus immediate early phosphoprotein pp89 Interferon-gamma Cysteine Endopeptidases Proteasome Endopeptidase Complex Psme1 protein, mouse
Topics	Amino Acid Sequence Animals Antigen Presentation (immunology, physiology) Autoantigens Base Sequence Blotting, Western Cell Line Cloning, Molecular Cysteine Endopeptidases (physiology) Cytomegalovirus (immunology) DNA Primers Enzyme Activation Flow Cytometry H-2 Antigens (immunology) Histocompatibility Antigen H-2D Humans Immediate-Early Proteins (genetics, immunology) Influenza A virus (immunology) Interferon-gamma (immunology) Mice Mice, Inbred BALB C Mice, Inbred C57BL Molecular Sequence Data Multienzyme Complexes (physiology) Muscle Proteins Proteasome Endopeptidase Complex Proteins (genetics, immunology, physiology) Recombinant Proteins (genetics, immunology) T-Lymphocytes, Cytotoxic (immunology) Transfection

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