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Titolo:
Prevention of passively transferred experimental autoimmune myasthenia gravis by a phage library-derived cyclic peptide
Autore:
Venkatesh, N; Im, SH; Balass, M; Fuchs, S; Katchalski-Katzir, E;
Indirizzi:
Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 Chem, IL-76100 Rehovot, Israel Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 unol, IL-76100 Rehovot, Israel
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 2, volume: 97, anno: 2000,
pagine: 761 - 766
SICI:
0027-8424(20000118)97:2<761:POPTEA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAIN IMMUNOGENIC REGION; NICOTINIC ACETYLCHOLINE-RECEPTOR; MONOCLONAL-ANTIBODIES; GENE-EXPRESSION; EPITOPE LIBRARY; ALPHA-SUBUNIT; MUSCLE; RESIDUES; IDENTIFICATION; SPECIFICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Katchalski-Katzir, E Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 t, Israel
Citazione:
N. Venkatesh et al., "Prevention of passively transferred experimental autoimmune myasthenia gravis by a phage library-derived cyclic peptide", P NAS US, 97(2), 2000, pp. 761-766

Abstract

Many pathogenic antibodies in myasthenia gravis (MG) and its animal model,experimental autoimmune MG (EAMG), are directed against the main immunogenic region (MIR) of the acetylcholine receptor (AcChoR). These antibodies are highly conformation dependent; hence, linear peptides derived from nativereceptor sequences are poor candidates for their immunoneutralization. We employed a phage-epitope library to identify peptide-mimotopes capable of preventing the pathogenicity of the anti-MIR mAb 198. We identified a 15-merpeptide (PMTLPENYFSERPYH) that binds specifically to mAb 198 and inhibits its binding to AcChoR. A 10-fold increase in the affinity of this peptide was achieved by incorporating flanking amino acid residues from the coat protein as present in the original phage library. This extended peptide (AEP-MTLPENYFSERPYHPPPP) was constrained by the addition of cysteine residues on both ends of the peptide, thus generating a cyclic peptide that inhibited the binding of mAb 198 to AcChoR with a potency that is three orders of magnitude higher when compared with the parent library peptide. This cyclic peptide inhibited the in vitro binding of mAb 198 to AcChoR and prevented the antigenic modulation of AcChoR caused by mAb 198 in human muscle cell cultures. The cyclic peptide also reacted with several other anti-MIR mAbs and the sera of EAMG rats. In addition, this peptide blocked the ability of mAb 198 to passively transfer EAMG in rats. Further derivatization of the cyclic peptide may aid in the design of suitable synthetic mimotopes for modulation of MG.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/06/20 alle ore 23:54:00