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Characterization of Desmoglein-3 Epitope Region Peptides as Synthetic Antigens: Analysis of their in vitro T-cell Stimulating Efficacy, Cytotoxicity, Stability and their Conformational Features

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Tartalom: http://real.mtak.hu/29966/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Unpublished



Type = Article
Cím:
Characterization of Desmoglein-3 Epitope Region Peptides as Synthetic Antigens: Analysis of their in vitro T-cell Stimulating Efficacy, Cytotoxicity, Stability and their Conformational Features
Létrehozó:
Szabados, Hajnalka
Uray, Katalin
Majer, Zsuzsa
Silló, Pálma
Kárpáti, Sarolta
Hudecz, Ferenc
Bősze, Szilvia
Dátum:
2015-08-06
Téma:
QD04 Organic chemistry / szerves kémia
QR180 Immunology / immunológia
RL Dermatology / bőrgyógyászat
Tartalmi leírás:
Desmoglein-3 (Dsg3) adhesion protein is the main target of autoantibodies and autoreactive T cells in Pemphigus vulgaris (PV) autoimmune skin disorder. Several mapping studies of Dsg3 T cell epitope regions were performed, and based on those data, we designed and synthesized four peptide series corresponding to Dsg3 T cell epitope regions. Each peptide series consists of a 17mer full-length peptide (Dsg3/189?205, Dsg3/206?222, Dsg3/342?358, and Dsg3/761?777) and its N-terminally truncated derivatives, resulting in 15 peptides altogether. The peptides were prepared on solid phase and were chemically characterized. In order to establish a structure?activity relationship, the solution conformation of the synthetic peptides has been investigated using electronic circular dichroism spectroscopy. The in vitro T cell stimulating efficacy of the peptides has been determined on peripheral blood mononuclear cells isolated from whole blood of PV patients and also from healthy donors. After 20h of stimulation, the interferon (IFN)-? content of the supernatants was measured by enzyme-linked immunosorbent assay. In the in vitro conditions, peptides were stable and non-cytotoxic. The in vitro IFN-? production profile of healthy donors and PV patients, induced by peptides as synthetic antigens, was markedly different. The most unambiguous differences were observed after stimulation with 17mer peptide Dsg3/342?358, and three truncated derivatives from two other peptide series, namely, peptides Dsg3/192?205, Dsg3/763?777, and Dsg3/764?777. Comparative analysis of in vitro activity and the capability of oligopeptides to form ordered or unordered secondary structure showed that peptides bearing high solvent sensibility and backbone flexibility were themost capable to distinguish between healthy and PV donors.
Típus:
Article
NonPeerReviewed
Formátum:
text
Azonosító:
Szabados, Hajnalka and Uray, Katalin and Majer, Zsuzsa and Silló, Pálma and Kárpáti, Sarolta and Hudecz, Ferenc and Bősze, Szilvia (2015) Characterization of Desmoglein-3 Epitope Region Peptides as Synthetic Antigens: Analysis of their in vitro T-cell Stimulating Efficacy, Cytotoxicity, Stability and their Conformational Features. JOURNAL OF PEPTIDE SCIENCE, 21 (9). pp. 731-742. ISSN 1075-2617 (Unpublished)
Kapcsolat:
https://dx.doi.org/10.1002/psc.2800