2-23 - Fc R polymorphism infuences response to therapeutic...

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Unformatted text preview: Fc R polymorphism infuences response to therapeutic antibodies. Human Fc RIIIa-158V binds IgG with higher anity than Fc RIIIa-158F . Lymphoma patients were treated with anti-CD20 humanized IgG1. Patients with Fc RIIIa-158V responded better than those with Fc RIIIa-158F. Improving the efFcacy of mAb Neutralization B cell Antigen activation Low afFnity antibody (IgM, IgG, IgA) AfFnity maturation High afFnity antibody (IgG, IgA) The most effective for neutralization Maternal IgG protect the baby. Maternal IgG is transported by FcRn (neonatal Fc receptor) across placental to the fetus. 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. FcRn is homologous to Class I MHC. Fc 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 FcRn defcient mice are unable to absorb maternal IgG orm 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 o 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...
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This note was uploaded on 03/25/2010 for the course BIO 360K taught by Professor Bryant during the Spring '09 term at University of Texas at Austin.

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2-23 - Fc R polymorphism infuences response to therapeutic...

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