PMID: 2125362Nov 1, 1990Paper

Enhancement of complement activation and cytolysis of human IgG3 by deletion of hinge exons

Scandinavian Journal of Immunology
T E MichaelsenI Sandlie

Abstract

The capacity to induce complement-mediated cell lysis is greatly enhanced by truncating the hinge of IgG3 through exon deletions. This was shown by establishing five new cell lines which secreted chimeric IgG3 molecules with specificity for the hapten 4-hydroxy-3-nitrophenacetyl (NP) and having 47,45,32,15, and 0 amino acid hinge regions (the wild-type IgG3 has 62 amino acids in the hinge). Efficient complement activation and complement-mediated cell lysis did not depend on a long total hinge or on a long 'upper' hinge (the stretch from the beginning of the hinge to the first inter-heavy chain S-S bond). On the contrary, the mutant having a 15 amino acid hinge element was up to 10 times more efficient in complement lysis than the wild type. Thus the complement-activation potential appeared to be down-regulated in the wild type. On the other hand, the mutant lacking the hinge altogether did not activate complement or induce complement-mediated cytolysis. These findings have to be taken into account when antibodies are designed for human therapy.

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Citations

Jul 18, 2001·Veterinary Immunology and Immunopathology·L TangC McCall
Jul 20, 1999·Kidney International·P M Ronco
Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·T E MichaelsenI Sandlie
Apr 28, 2012·Nucleic Acids Research·Nicolay R NilssenGeir Å Løset
Oct 19, 2013·Journal of Pharmaceutical Sciences·Roxana E IacobDamian Houde
Jul 16, 2011·Molecular Immunology·Nina A DahaLeendert A Trouw
Nov 13, 2009·Scandinavian Journal of Immunology·T E MichaelsenO Ihle
Mar 10, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Torunn Elisabeth TjelleBjarne Bogen
Nov 20, 2016·Scandinavian Journal of Immunology·T E MichaelsenI Sandlie
Dec 23, 1999·International Immunology·V SørensenI Sandlie
Nov 1, 1991·European Journal of Immunology·E G RoutledgeH Waldmann
Feb 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Geir Å LøsetInger Sandlie
Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Morten FlobakkInger Sandlie
Jun 29, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Thies RösnerStefanie Derer
Jul 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·William F Dall'AcquaHerren Wu
May 1, 1993·European Journal of Immunology·J GreenwoodH Waldmann
May 22, 2020·Frontiers in Immunology·Steven W de TaeyeGestur Vidarsson
Feb 20, 2021·MAbs·Thach H ChuMargaret E Ackerman

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