Thanks to a custom-designed receptor, this killer T-cell slays HIV-infected cells far better than normal T-cells do (Image: Andrew Sewell/University of Oxford) HIV’s SL9 molecule’s (red) fits snuggly into the engineered receptor (grey) (Illustration: Andrew Sewell/University of Oxford)

Researchers have harnessed evolution to create souped-up immune cells able to recognise HIV far better than the regular “killer” T-cells our body produces.

The pimped up T-cell boasts a molecular receptor evolved in the lab to give the body the edge against a virus that has so far flummoxed our immune systems.


“When the body gets infected with HIV, the immune system doesn’t know what the virus is going to do – but we do,” says Andrew Sewell, an immunologist at Cardiff University, UK, who led the study.

One reason HIV has been able to skirt our immune systems, drugs and vaccines is the virus’s chameleon-like behaviour – thanks to a genome that mutates with ease, HIV can quickly change guise to evade an attack.

But some parts of HIV are so vital to its functioning that changes result in dead or severely compromised viruses. Sewell’s team targeted a part of one such protein, which holds the virus together.

The virus normally hides this protein from our immune system. But when HIV infects cells, small bits of this protein get trapped on the surface, warning the immune system of the danger that lurks inside.

The problem is that the killer T-cells our bodies produce do a mediocre job of recognizing SL9, Sewell says. So his team designed super T-cells that could recognize a portion of the protein called SL9, and then destroy the infected cell – thus preventing the virus from spreading.

Evolved killers

Beginning with a particularly potent T-cell collected from a patient in 1996, Sewell’s team sought to redesign the receptor molecule that recognizes SL9.

This was done by letting one of evolution’s guiding principles – survival of the fittest – take hold. In this case, the researchers selected for mutated receptors that grabbed the tightest to SL9.

In a Petri dish, the customised T-cells outperformed normal T-cells, slaying virus-infected cells with ease.

The pimped up T-cells produced high levels of chemicals, called cytokines, which are indicative of a successful immune response. The engineered cells also recognised variations on SL9 that befuddle normal killer T-cells.

Sewell’s team is preparing to test the cells in mice that have been engineered to produce human immune cells, capable of becoming infected with HIV. If those tests go well, his team hopes to try the approach in HIV-infected people.

Side effects?

One pitfall could be that the cells prove too strong for their own good, says James Riley, an immunologist at the University of Pennsylvania in Philadelphia, who also led the study.

The cells might be designed to see only SL9, but there is a chance they could recognise and attack human proteins, he says.

“The big concern is autoimmunity – that these things will not only recognise things that we want, but they will also recognise things that we don’t want them to,” he says.

But with the recent failure of one major HIV vaccine trial and the cancellation of another, researchers are in a soul-searching mood, says Philip Goulder, an immunologist at the University of Oxford.

“I think the field as a whole has been taking a step back and thinking we need some different ideas all together,” he says.

And while an expensive therapy that involves genetically engineering cells from a patient then re-injecting them back may never be feasible in sub-Saharan Africa, the approach could help researchers come up with more effective vaccines and therapeutics, Goulder says.

Journal reference: Nature Medicine (DOI: 10.1038/nm.1779)