This is mouse-human chimeric IgG1 and 3 variants harboring human heavy chains and mouse lambda light chains with specificity for the hapten NIP (4-hydroxy-3-iodo-5-nitrophenylacetic acid). In addition to the WT variants, a panel of IgG1 Fc mutated variants is listed.
IgG1 with the N297A mutation removes the N-glycosylation motif and thus eliminates binding to the classical Fc gamma receptors. The IgG1 mutants H310A, H435A and H310A/H435A modulate or eliminate binding to the neonatal Fc receptor (FcRn).
The IgG1 antibodies with combination of mutations have been made based on published papers describing Fc- mutant variants with improved binding to human FcRn, however, here we have produced them with the same framework and specificity. The IgG1 variant containing M252Y/S254T/T246E/H433K/N434F (MST/HN) is a so-called “abdeg” molecule, which binds the receptor more strongly at both acidic as well as neutral pH and thus acts as a blocker for binding of competing IgG. IgG1-M252Y/S254T/T246E (MST or YTE), IgG1-H433K/N434F (MN) and IgG1-H433K/N434F (HN) contain Fc-mutations that improve pH dependent binding to FcRn, which give rise to extended serum half-life.
Construction of the anti-NIP antibodies is described here:
Grevys A, Bern M, Foss S, Bratlie DB, Moen A, Gunnarsen KS, Aase A, Michaelsen TE, Sandlie I, Andersen JT. J Immunol. 2015 Jun 1;194(11):5497-508
References to the original papers describing the mutations are given in this publication.
IgG1-E318A/E345A, IgG1-E345A, IgG1-E318A, IgG1-H285A, IgG1-H268A harbor mutations at the positions indicated in the Fc domains.
