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Titolo:
Overexpression of the proteasome subunits LMP2, LMP7, and MECL-1, but not PA28 alpha/beta, enhances the presentation of an immunodominant lymphocyticchoriomeningitis virus T cell epitope
Autore:
Schwarz, K; van den Broek, M; Kostka, S; Kraft, R; Soza, A; Schmidtke, G; Kloetzel, PM; Groettrup, M;
Indirizzi:
Kantonsspital, Lab Forsch Abt, Dept Res, CH-9007 St Gallen, Switzerland Kantonsspital St Gallen Switzerland CH-9007 -9007 St Gallen, Switzerland Univ Zurich Hosp, Dept Pathol, Inst Expt Immunol, CH-8091 Zurich, Switzerland Univ Zurich Hosp Zurich Switzerland CH-8091 CH-8091 Zurich, Switzerland Max Delbruck Ctr Mol Med, Berlin, Germany Max Delbruck Ctr Mol Med Berlin Germany ck Ctr Mol Med, Berlin, Germany Humboldt Univ, Fac Med Charite, Inst Biochem, Berlin, Germany Humboldt Univ Berlin Germany Med Charite, Inst Biochem, Berlin, Germany
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 2, volume: 165, anno: 2000,
pagine: 768 - 778
SICI:
0022-1767(20000715)165:2<768:OOTPSL>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAJOR HISTOCOMPATIBILITY COMPLEX; I ANTIGEN PRESENTATION; 20S PROTEASOME; INTERFERON-GAMMA; IFN-GAMMA; ENDOPLASMIC-RETICULUM; BETA-SUBUNITS; ALPHA-SUBUNIT; ACTIVE-SITE; REG-ALPHA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
64
Recensione:
Indirizzi per estratti:
Indirizzo: Groettrup, M Kantonsspital, Lab Forsch Abt, Dept Res, Haus 09, CH-9007 St Gallen, Switzerland Kantonsspital Haus 09 St Gallen Switzerland CH-9007 tzerland
Citazione:
K. Schwarz et al., "Overexpression of the proteasome subunits LMP2, LMP7, and MECL-1, but not PA28 alpha/beta, enhances the presentation of an immunodominant lymphocyticchoriomeningitis virus T cell epitope", J IMMUNOL, 165(2), 2000, pp. 768-778

Abstract

The proteasome is a large protease complex that generates most of the peptide ligands of MHC class I molecules either in their final form or in the form of N-terminally extended precursors. Upon the stimulation of cells withIFN-gamma, three constitutively expressed subunits of the 20S proteasome are replaced by the inducible subunits LMP2 (low-molecular mass polypeptide 2), LMP7, and MECL-1 (multicatalytic endopeptidase complex-like-1) to form so-called immunoproteasomes. We show in this study that overexpression of these three subunits in triple transfectants led to a marked enhancement in the H-2L(d)-restricted presentation of the immunodominant nonameric epitopeNP118, which is derived from the nucleoprotein (NP) of lymphocytic choriomeningitis virus. Overexpression of the alpha and beta subunits of the IFN-gamma-inducible proteasome regulator PA28, in contrast, did not have a comparable effect. In vitro, immunoproteasomes as compared with constitutive proteasomes generated higher amounts of 11- and 12-mer fragments containing the NP118 epitope, These are likely to be cytosolic precursors of NP118, as aproline anchor residue in the second position of NP118 may interfere with TAP-mediated transport, of the nonameric epitope itself. In conclusion, we provide evidence that up-regulation of the three inducible subunits, LMP2, LMP7, and MECL-1, can result in a marked improvement of Ag presentation andthat, depending on the epitope, PA28 and immunoproteasomes may differentially affect Ag processing.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 10:38:27