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HIV is an unrelenting virus that hijacks and destroys the human immune system from within, leading to inevitable death in almost all cases. But for a group of rare patients, called HIV controllers, their natural systems have a way to keep the virus from complete victory.

The secret recipe of controller success is a group of super receptors on key immune cells, allowing them to fight of the virus, according to a new paper in the journal Science Immunology.

“We establish the mechanistic basis underpinning this broad cross-restriction and show that these public (T cell receptors) have cytotoxic capacity and kill HIV-infected cells,” the team, led by scientists at Monash University and the Pasteur Institute in Paris, writes.

The location of the receptors is on the CD4 T cells that are usually considered as helpers for their killer CD8 T counterparts.

The immune advantage was found and catalogued in 15 HIV-positive patients, using the Australian Synchrotron, to assess the binding of the special T cells sites to the HIV-triggered Human Leukocyte Antigen.

Running experiments to understand how the CD4 cells respond to the virus, they found HIV controllers’ immune response functioned a bit differently, according to Stephanie Gras, one of the authors from Monash University.

“We discovered that those CD4 T cells, usually viewed as helper cells for the killer CD8 T cells that destroy infected cells, could be turned into killer cells themselves in HIV controllers,” Gras said. “These killer CD4+ could recognize very low amounts of HIV thanks to the expression of super T cell receptors on their surface.”

The tiny biological quirk was common to the controllers, Gras said.

“Importantly, when they studied these receptors, they found identical receptors across multiple HIV controllers,” she said.

Previous studies stretching back a decade and more had focused on targets like the HLA-B protein, among other links in the immunological chain of events.

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