In the hunt for a vaccine for human immunodeficiency virus, or HIV, scientists have provided a first-ever glimpse of the structure of a key protein that could help them understand how to build a better vaccine.
Researchers at the California Institute of Technology demonstrated that a particular antibody to the protein gp120 makes contact with the protein and the CD4 receptor that gp120 uses to gain entrance into the body's T cells.
Most people who contract HIV and proceed to AIDS are infected with one member from the HIV-1 family of viruses. HIV-1 is divided into groups, and most AIDS-related strains of the virus come from group M. Those groups are subdivided into what are known as clades.
Clade B is the best-studied division, most often found in the United States and western Europe.
Led by professor Pamela Bjorkman, the Caltech team looked at gp120 from what is known as clade C, the division prevalent in Africa and Asia.
What they found surprised them.
To reveal the structure of clade C gp120 -- which was assumed to be similar to clade B -- the Caltech team needed to crystallize the protein. But it was not stiff enough for the task.
To accomplish this, the researchers created a complex of molecules (a gp120 monomer, a CD4 receptor and an anti-HIV antibody known as 21c, if you were wondering) that facilitated the process.
That allowed the researchers to visualize the entire binding site and see how the each component in the complex interacted with the others.
What they found, however, is that antibody 21c was reacting with both the gp120 protein and the CD4 receptors on the body's own T cells.
The phenomenon is called "polyreactivity," and it's the first time it has been visualized in the three-dimensional structure of an HIV-targeting antibody.
That suggests that this class of anti-HIV antibodies has autoreactive properties, prompting new questions about the implications of how the body's immune system responds to HIV.
Tn an attempt to keep autoimmune diseases at bay, the body tends to eliminate autoreactive antibodies -- meaning a successful vaccine would have to overcome this mechanism to work effectively.
For now, the Caltech team plans to improve on its low-resolution structure detailed in the current paper, as well as attempt to resolve the structure of a "gp120 trimer," a more complex version of the protein.
"There's a tremendous continuing effort to develop a vaccine for HIV," postdoctoral scholar Ron Diskin said in a statement. "Most of those efforts use gp120. Having more structural information will facilitate better vaccine design."
Their research was published in the online edition of the journal Nature Structural & Molecular Biology.
This post was originally published on Smartplanet.com