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Caltech scientists uncover structure of key protein in common HIV subgroup
Date:4/2/2010

rystallize the protein. That was no easy task. Turns out, says Diskin, the protein itself is not stiff enough for crystallization. And so the researchers created a complex of molecules consisting of a gp120 monomer, a CD4 receptor, and an anti-HIV antibody known as 21c.

This configuration facilitated crystallization, and allowed the scientists to look not only at gp120which, indeed, "looks pretty much the same in clade C as in clade B," says Diskinbut to visualize the entire binding site and to see how the various components in the complex interact with one another.

That was when they noticed something unusual: Antibody 21c was not only reacting toand thus making contact withthe gp120 protein sticking out from HIV's envelope, but also was reacting to the CD4 receptors on the body's own T cells. It is the first time this sort of polyreactivitya response to more than one antigenhad been visualized in the 3-D structure of an HIV-targeting antibody.

"The most interesting aspect of our structure is the unexpected contact between the antibody and CD4," says Pamela Bjorkman, the Max Delbruck Professor of Biology at Caltech, a Howard Hughes Medical Institute investigator, and the Caltech team's leader. "The binding to CD4 suggests that this class of anti-HIV antibodies has autoreactive properties, which raises many interesting questions about how anti-HIV immune responses affect an HIV-infected individual."

Does this autoreactivity mean that 21c is too dangerous to work with, because clinicians might be courting a potential autoimmune response with a vaccine that elicits 21c-like antibodies?

Not necessarily, says Diskin.

"Other data out there show that some of the best neutralizing antibodies are also autoreactive," he explains.

What it does mean, however, is that there would be additional hurdles to overcome in eliciting such antibody responses, Diskin says. The body tends to eliminate autoreactive antibodies
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Contact: Lori Oliwenstein
lorio@caltech.edu
626-395-3631
California Institute of Technology
Source:Eurekalert  

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