Journal
MOLECULAR IMMUNOLOGY
Volume 63, Issue 2, Pages 456-463Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2014.09.017
Keywords
Mouse IgG2a; Fc silencing mutations; Mouse Fc gamma Rs binding; Complement
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The effects of the Fc silencing mutations such as leucine (L) to alanine (A) substitution at the position 234 and 235 (LALA) and the alanine (A) to asparagine (N) substitution at position 297 (N297A) are well investigated for human IgG. However, the effects of the same two silencing Fc mutations in a mouse IgG backbone are not yet well investigated in respect to binding to mouse Fc gamma receptors (Fc gamma Rs), complement and subsequent effector functions. By using a mouse IgG2a tool antibody directed against mouse OX40L, we demonstrate a strongly reduced binding of the two Fc mutants to high and low affinity recombinant and cell expressed mouse Fc gamma Rs, when compared to the mouse IgG2a with the wild type (wt) backbone. Reduced Fc gamma R binding by the two investigated Fc mutants could further be confirmed on primary mouse macrophages expressing their native Fc gamma Rs. In addition, we reveal that the LALA and N297A mutations in the mIgG2a also slightly reduced binding to C1 q of human origin. Thus, here we provide experimental evidence that the two investigated Fc mutations in the mouse IgG backbone lead to similar silencing properties as previously demonstrated for the human IgG and thus represent a useful method to alter effector functions in tool antibodies to be used in mouse models. (C) 2014 Elsevier Ltd. All rights reserved.
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