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Functional consequences of allotypic polymorphisms in human immunoglobulin G subclasses.


ABSTRACT: Heritable polymorphisms within the human IgG locus, collectively termed allotypes, have often been linked by statistical associations, but rarely mechanistically, to a wide range of disease states. One potential explanation for these associations is that IgG allotype alters host cell receptors' affinity for IgG, dampening or enhancing an immune response depending on the nature of the change and the receptors. In this work, a panel of allotypic antibody variants were evaluated using multiplexed, label-free biophysical methods and cell-based functional assays to determine what effect, if any, human IgG polymorphisms have on antibody function. While we observed several differences in FcγR affinity among allotypes, there was little evidence of dramatically altered FcγR-based effector function or antigen recognition activity associated with this aspect of genetic variability.

SUBMITTER: Crowley AR 

PROVIDER: S-EPMC9845132 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Functional consequences of allotypic polymorphisms in human immunoglobulin G subclasses.

Crowley Andrew R AR   Richardson Simone I SI   Tuyishime Marina M   Jennewein Madeleine M   Bailey Meredith J MJ   Lee Jiwon J   Alter Galit G   Ferrari Guido G   Morris Lynn L   Ackerman Margaret E ME  

Immunogenetics 20220729 1


Heritable polymorphisms within the human IgG locus, collectively termed allotypes, have often been linked by statistical associations, but rarely mechanistically, to a wide range of disease states. One potential explanation for these associations is that IgG allotype alters host cell receptors' affinity for IgG, dampening or enhancing an immune response depending on the nature of the change and the receptors. In this work, a panel of allotypic antibody variants were evaluated using multiplexed,  ...[more]

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