The Shark Strikes Twice: Hypervariable Loop 2 of Shark IgNAR Antibody Variable Domains and Its Potential to Function as an Autonomous Paratope.
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Authors
Zielonka, StefanEmpting, Martin
Könning, Doreen
Grzeschik, Julius
Krah, Simon
Becker, Stefan
Dickgießer, Stephan
Kolmar, Harald

Issue Date
2015-08
Metadata
Show full item recordAbstract
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.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.Affiliation
2Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany.PubMed ID
26003538Type
ArticleLanguage
enISSN
1436-2236ae974a485f413a2113503eed53cd6c53
10.1007/s10126-015-9642-z
Scopus Count
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