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Titolo:
An altered peptide ligand inhibits the activities of matrix metalloproteinase-9 and phospholipase C, and inhibits T cell interactions with VCAM-1 induced in vivo by a myasthenogenic T cell epitope
Autore:
Faber-Elmann, A; Grabovsky, V; Dayan, M; Sela, M; Alon, R; Mozes, E;
Indirizzi:
Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 unol, IL-76100 Rehovot, Israel
Titolo Testata:
FASEB JOURNAL
fascicolo: 1, volume: 15, anno: 2001,
pagine: 187 - 194
SICI:
0892-6638(200101)15:1<187:AAPLIT>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
LYMPHOCYTE ANTIGEN RECEPTORS; ACETYLCHOLINE-RECEPTOR; AUTOIMMUNE-RESPONSE; SIGNAL-TRANSDUCTION; ADHESION MOLECULES; INTEGRIN VLA-4; ALPHA-SUBUNIT; GRAVIS; ANALOGS; FLOW;
Keywords:
autoimmune myasthenia gravis; T cell receptor; immunomodulation; T cell adhesiveness;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Mozes, E Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 76100 Rehovot, Israel
Citazione:
A. Faber-Elmann et al., "An altered peptide ligand inhibits the activities of matrix metalloproteinase-9 and phospholipase C, and inhibits T cell interactions with VCAM-1 induced in vivo by a myasthenogenic T cell epitope", FASEB J, 15(1), 2001, pp. 187-194

Abstract

Myasthenia gravis (MG) is a T cell-regulated, antibody-mediated autoimmunedisease. Immunization with two myasthenogenic peptides, p195-212 and p259-271, which are sequences of the human acetylcholine receptor, resulted in MG-associated immune responses. A dual altered peptide ligand (APL) composedof the two APLs of the myasthenogenic peptides inhibited, in vitro and in vivo, those responses. This study was aimed at understanding the mechanism(s) underlying the in vivo inhibitory properties of the dual APL. To this end, we analyzed T cells of mice that were immunized with p259-271 for their adhesiveness toward vascular cell adhesion molecule 1, for the activity of their secreted matrix metalloproteinases (MMPs), and for their intracellular phospholipase C (PLC) activity. Immunization with p259-271 triggered the above three activities and in vivo administration of the dual APL inhibitedthe latter. Thus, treatment of mice with the dual APL interferes with functions required for T cells to migrate and interact with the self-AChR. Thisis the first indication that very late antigen 4, MMP-9, and PLC are targets for immunomodulation of autoreactive T cells by altered peptide ligands.

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Documento generato il 25/09/20 alle ore 22:15:21