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Gewählte Publikation:

Kainer, M; Antes, B; Wiederkum, S; Wozniak-Knopp, G; Bauer, A; Ruker, F; Woisetschlager, M.
(2012): Correlation between CD16a binding and immuno effector functionality of an antigen specific immunoglobulin Fc fragment (Fcab)
ARCH BIOCHEM BIOPHYS. 2012; 526(2): 154-158. FullText FullText_BOKU

Antigen binding immunoglobulin Fc fragments (Fcab) are generated by engineering loop regions in the CH3 domain of human IgG1 Fc. Variants of an Fcab specific for Her-2 were designed to display either enhanced (S239D:A330L:I332E) or diminished (L234A:L235A) binding affinities to the Fc receptor CD16a based on mutations described previously. The two mutant Fcab proteins demonstrated the expected modulation of CD16a binding. Interaction with recombinant or cell surface expressed Her-2 was unaffected in both mutants compared to the parental Fcab. Binding affinities for CD16a correlated with the ADCC-potencies of the Fcab variants. Additional studies indicated that the L234A:L235A variant Fcab had equivalent structural features as the unmodified Fcab since their DSC profiles were similar and antigen binding after re-folding upon partial heat denaturation had not changed. Introduction of the S239D:A330L:I332E mutations resulted in a significant reduction of the CH2 domain melting temperature, a moderate decrease of the thermal transition of the CH3 domain and lower antigen binding after thermal stress compared to the parental Fcab. We conclude that the known correlation between CD16a binding affinity and ADCC potency is also valid in Fcab proteins and that antigen specific Fcab molecules can be further engineered for fine tuning of immuno effector functions. (C) 2012 Elsevier Inc. All rights reserved.
Autor*innen der BOKU Wien:
Rüker Florian
Wozniak-Knopp Gordana
Find related publications in this database (using NML MeSH Indexing)
Antibody-Dependent Cell Cytotoxicity -
Cell Line -
Cells, Cultured -
Humans -
Immunoglobulin Fc Fragments - chemistry
Immunoglobulin G - chemistry
Models, Molecular -
Point Mutation -
Protein Structure, Tertiary -
Receptor, erbB-2 - immunology
Receptors, IgG - immunology

Find related publications in this database (Keywords)
Fc fragment
Fc receptor binding

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