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2-23 - F c R p o ly m o r p h is m in u e n c e s r e s p o...

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Fc γ R polymorphism influences response to therapeutic antibodies. Human Fc γ RIIIa-158V binds IgG with higher affinity than Fc γ RIIIa-158F . Lymphoma patients were treated with anti-CD20 humanized IgG1. Patients with Fc γ RIIIa-158V responded better than those with Fc γ RIIIa-158F.
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Improving the efficacy of mAb
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Neutralization B cell Antigen activation Low affinity antibody (IgM, IgG, IgA) Affinity maturation High affinity antibody (IgG, IgA) The most effective for neutralization
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Maternal IgG protect the baby. Maternal IgG is transported by FcRn (neonatal Fc receptor) across placental to the fetus.
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FcRn-IgG interaction is regulated by pH. mouse human FcRn binds IgG at pH<6.5, and dissociates from IgG at pH7.4.. IgG is transported from maternal blood into fetal circulation in placenta. IgG is transported from maternal milk into the intestine of neonatal mice.
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FcRn is homologous to Class I MHC. Fc γ RIII Glu COO - FcRn N + N H His Fc pKa=6.0 pH<6.5 Glu COO - FcRn N N His Fc pH>7.0 association dissociation Salt bridge interactions
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FcRn deficient mice are unable to absorb maternal IgG form milk. Anti-TNP IgG was injected into Pregnant mice at day 17. Anti-TNP IgG was measured in 3-day old pups. FcRn extends the t 1/2 of IgG Non-IgG t 1/2 : 1-2 days IgG t 1/2 : 6-8 days (mice); 22-23 days (human) Anti-TNP IgG or IgA was injected into 6-7 weeks old Mice.
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