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Publication Date
5-2021
Abstract
Individuals have variable response to vaccination and immunotherapy that may be attributable to host genetics. A critical yet often overlooked mechanism driving vaccine and immunotherapy efficacy are immunoglobulin (Ig) constant region fragment crystallizable (Fc) effector functions that are critical for antibody stability and effector immune cell function. Our group will thus incorporate genomic, molecular biology and biochemical methods to investigate how Fc variance may impact Fc receptor (FcR) binding kinetics. We have established a next-generation sequencing analysis pipeline to identify and characterize genetic variance in the Ig constant region in various human populations. We will then engineer the observed variants into therapeutic monoclonal antibodies to determine the Fc:FcR binding kinetics of these natural and artificial Ig allotypes using Surface Plasmon Resonance – a highly sensitive biochemical application used to evaluate Receptor/Ligand binding kinetics in an in vitro environment. Finally, we will utilize cell-based functionality assays to determine the extent to which difference in binding kinetics impacts Fc:FcR effector function. Our experimental plan will thus provide us with conclusive data concerning Fc genetic variance, if specific SNP’s can impact Fc:FcR binding kinetics, and if this ultimately would impact Fc:FcR driven effector functions.
Document Type
Poster
Recommended Citation
Pierce, Stephen; Khanal, Santosh; and Bradley, Todd, "The Impact Of Antibody Fc Region Genetic Variance On Humoral Immunity" (2021). Research at Children's Mercy Month 2021. 5.
https://scholarlyexchange.childrensmercy.org/research_month2021/5
