The Shark Strikes Twice: Hypervariable Loop 2 of Shark IgNAR Antibody Variable Domains and Its Potential to Function as an Autonomous Paratope.

2.50
Hdl Handle:
http://hdl.handle.net/10033/561055
Title:
The Shark Strikes Twice: Hypervariable Loop 2 of Shark IgNAR Antibody Variable Domains and Its Potential to Function as an Autonomous Paratope.
Authors:
Zielonka, Stefan; Empting, Martin ( 0000-0002-0503-5830 ) ; Könning, Doreen; Grzeschik, Julius; Krah, Simon; Becker, Stefan; Dickgießer, Stephan; Kolmar, Harald
Abstract:
In this present study, we engineered hypervariable loop 2 (HV2) of the IgNAR variable domain in a way that it solely facilitates antigen binding, potentially functioning as an autonomous paratope. For this, the surface-exposed loop corresponding to HV2 was diversified and antigen-specific variable domain of IgNAR antibody (vNAR) molecules were isolated by library screening using yeast surface display (YSD) as platform technology. An epithelial cell adhesion molecule (EpCAM)-specific vNAR was used as starting material, and nine residues in HV2 were randomized. Target-specific clones comprising a new HV2-mediated paratope were isolated against cluster of differentiation 3ε (CD3ε) and human Fcγ while retaining high affinity for EpCAM. Essentially, we demonstrate that a new paratope comprising moderate affinities against a given target molecule can be engineered into the vNAR scaffold that acts independent of the original antigen-binding site, composed of complementarity-determining region 3 (CDR3) and CDR1.
Affiliation:
2Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany.
Citation:
The Shark Strikes Twice: Hypervariable Loop 2 of Shark IgNAR Antibody Variable Domains and Its Potential to Function as an Autonomous Paratope. 2015, 17 (4):386-92 Mar. Biotechnol.
Journal:
Marine biotechnology (New York, N.Y.)
Issue Date:
Aug-2015
URI:
http://hdl.handle.net/10033/561055
DOI:
10.1007/s10126-015-9642-z
PubMed ID:
26003538
Type:
Article
Language:
en
ISSN:
1436-2236
Appears in Collections:
publications of the department drug design and optimization (HIPS]DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorZielonka, Stefanen
dc.contributor.authorEmpting, Martinen
dc.contributor.authorKönning, Doreenen
dc.contributor.authorGrzeschik, Juliusen
dc.contributor.authorKrah, Simonen
dc.contributor.authorBecker, Stefanen
dc.contributor.authorDickgießer, Stephanen
dc.contributor.authorKolmar, Haralden
dc.date.accessioned2015-07-27T09:50:38Zen
dc.date.available2015-07-27T09:50:38Zen
dc.date.issued2015-08en
dc.identifier.citationThe Shark Strikes Twice: Hypervariable Loop 2 of Shark IgNAR Antibody Variable Domains and Its Potential to Function as an Autonomous Paratope. 2015, 17 (4):386-92 Mar. Biotechnol.en
dc.identifier.issn1436-2236en
dc.identifier.pmid26003538en
dc.identifier.doi10.1007/s10126-015-9642-zen
dc.identifier.urihttp://hdl.handle.net/10033/561055en
dc.description.abstractIn this present study, we engineered hypervariable loop 2 (HV2) of the IgNAR variable domain in a way that it solely facilitates antigen binding, potentially functioning as an autonomous paratope. For this, the surface-exposed loop corresponding to HV2 was diversified and antigen-specific variable domain of IgNAR antibody (vNAR) molecules were isolated by library screening using yeast surface display (YSD) as platform technology. An epithelial cell adhesion molecule (EpCAM)-specific vNAR was used as starting material, and nine residues in HV2 were randomized. Target-specific clones comprising a new HV2-mediated paratope were isolated against cluster of differentiation 3ε (CD3ε) and human Fcγ while retaining high affinity for EpCAM. Essentially, we demonstrate that a new paratope comprising moderate affinities against a given target molecule can be engineered into the vNAR scaffold that acts independent of the original antigen-binding site, composed of complementarity-determining region 3 (CDR3) and CDR1.en
dc.language.isoenen
dc.titleThe Shark Strikes Twice: Hypervariable Loop 2 of Shark IgNAR Antibody Variable Domains and Its Potential to Function as an Autonomous Paratope.en
dc.typeArticleen
dc.contributor.department2Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany.en
dc.identifier.journalMarine biotechnology (New York, N.Y.)en

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