Mutations within a human IgG2 antibody form distinct and homogeneous disulfide isomers but do not affect Fc gamma receptor or C1q binding.

Protein Science : a Publication of the Protein Society
Sandra LightleTheodore Oliphant

Abstract

Human IgG2 antibodies may exist in at least three distinct structural isomers due to disulfide shuffling within the upper hinge region. Antibody interactions with Fc gamma receptors and the complement component C1q contribute to immune effector functions. These interactions could be impacted by the accessibility and structure of the hinge region. To examine the role structural isomers may have on effector functions, a series of cysteine to serine mutations were made on a human IgG2 backbone. We observed structural homogeneity with these mutants and mapped the locations of their disulfide bonds. Importantly, there was no observed difference in binding to any of the Fc gamma receptors or C1q between the mutants and the wild-type IgG2. However, differences were seen in the apparent binding affinity of these antibodies that were dependent on the selection of the secondary detection antibody used.

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Citations

Jun 15, 2011·Pharmaceutical Research·Xiaoling WangSatish K Singh
Mar 14, 2013·Journal of the American Society for Mass Spectrometry·Lisa M JonesMichael L Gross
Jun 14, 2013·PloS One·Sergey RyazantsevVladimir Zav'yalov
Nov 5, 2014·Frontiers in Immunology·Gestur VidarssonTheo Rispens
Nov 26, 2013·Veterinary Immunology and Immunopathology·Lisa M BergeronGraeme Bainbridge
Feb 25, 2014·Veterinary Immunology and Immunopathology·Catherine J StrietzelGraeme Bainbridge
Dec 20, 2017·Analytical and Bioanalytical Chemistry·Jude C LakbubHeather Desaire
Feb 20, 2021·MAbs·Thach H ChuMargaret E Ackerman

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