Mouquet Notes

Mouquet Notes - "Polyreactivity increases the apparent...

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"Polyreactivity increases the apparent affinity of anti-HIV antibodies by hetroligation" Mouquet et al -gp140 glycoprotein spikes on HIV disfavors homotypic bivalent antibody binding -somatic mutations of antibodies increase affinity, breadth and neutralization potency -B Cells produce polyreactive Abs, bivalent heteroligation between one high-affinity anti-HIV-gp140 combining site and a second low-affinity site on a another HIV molecule. -cross-reactivity to self-antigens or polyreactivity is common in HIV, Epstein-Barr and HepC viruses, even though it is normally selected against. -75% of 134 anti-HIV-gp140 antibodies cloned from six patients are polyreactive -The possible function for polyreactivity would be to increase affinity where simple homotypic bivalent ligation is not feasible (like when?). -Ex. 1: HIV gp140 surface spike, low density (10-15 viral spikes per virion). Homotypic bivalent binding is unlikely, but heteroligation might increase affinity to virus. One high-affinityto gp140 and one low-affinity to somewhere else on virus. -studied 134 unique anti-gp140 and 52 control non-gp140 Abs Supp Table1. -test binding to ssDNA, dsDNA, lipopolysaccharide, insulin, keyhole limpet haemocyanin (KLH) using ELISAs. -59-82% polyreactivity of anti-HIV Abs among each patient, but 75% overall. -apparently a huge difference between gp140 binding and non-binding Abs (Fig. 1b, Supp Fig. 1A) -also measured cardiolipin binding (fig. 1C) and to self-antigens in HEp-2 cell lysates (fig. 1D) -So, they must be measuring the "color" change or OD 405 to quantify binding -How can they say the horizontal line corresponding OD405 ~0.5 is the positive reactivity threshold? Is
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This note was uploaded on 06/08/2011 for the course CHEM 209 taught by Professor Ghosh,g during the Spring '08 term at UCSD.

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Mouquet Notes - "Polyreactivity increases the apparent...

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