Polymorphic variants of Fc receptors and antibodies derived from humans and rhesus macaques exhibit differential binding

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2017-05-12

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Abstract

Immune effector functions often depend on the fragment crystallizable (Fc) region of antibodies binding with Fc receptors (FcRs) on immune cells to trigger various responses. Polymorphisms in both Fc and FcR genes in humans and rhesus macaques have been demonstrated to alter the strength of this binding and consequently the immune response that is elicited. Rhesus macaques are often studied as an animal model for AIDS-like diseases, although he diversity of their FcRs has not yet been well characterized. Rhesus have more variation in their FcR genes, but less variation among IgG subclasses compared to humans. I hypothesize that the strength of signaling and subsequent immune responses caused by FcR-bearing cells will be regulated by the strength of Fc binding and the expression levels of FcRs on effector cells. To test this hypothesis, a more accurate genome map of human and rhesus macaques must be compiled, and methods developed to characterize interactions between polymorphic variants of FcRs and antibodies. I devised an ELISA protocol to test the hypothesis that known human and rhesus macaque FcR polymorphisms have differing binding affinities to antibody variants. My results suggest that ELISA assays can measure the strength of binding between variants of FcRs and antibodies to characterize interactions between these molecules. Future work should use similar ELISA techniques as well as immune complexes suspended in solution to distinguish the differing responses among a wider variety of both human and macaque polymorphisms within both FcR and antibody genes.

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Penny, Caitlin (2017). Polymorphic variants of Fc receptors and antibodies derived from humans and rhesus macaques exhibit differential binding. Honors thesis, Duke University. Retrieved from https://hdl.handle.net/10161/14334.


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