Could a Super Receptor Be the Answer to Eradicating HIV?

Although treatments for HIV allow patients to live with the disease, there is still no therapy that can eradicate the virus across a genetically different population.

Researchers have discovered a receptor on immune cells that may be the answer to eradicating HIV, according to a study published in Science Immunology.

The study evaluated 15 unique patients known as HIV controllers. Although these patients are infected with HIV, their immune systems are capable of protecting them from progressing to AIDS. Their incredibly rare ability to control the virus could provide researchers with clues that lead to a potential cure, according to the study.

Patients with HIV experience a depletion in CD4 T cells, which play a vital role in a healthy immune system. HIV progresses to AIDS as the CD4 T cells continue to drop and a patient’s immunity deteriorates, according to the study.

Antiretroviral therapy (ART) can be used to prevent AIDS progression, with more than half of those with HIV globally receiving the therapy, according to the study. Although patients receiving ART have a decreased risk of mortality, they cannot be completely cured of HIV and still experience low CD4 T cell counts.

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The researchers found that HIV controllers retained high quality CD4 T cells that could detect and fight off traces of the virus. They also found identical receptors among all HIV controllers.

"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,” Stephanie Gras, PhD, associate professor of biochemistry and molecular biology, said in a press release. “These killer CD4+ T cells could recognize very low amounts of HIV thanks to the expression of "super" T cell receptors on their surface. Importantly when they studied these receptors—they found identical receptors across multiple HIV controllers.”

T cells can recognize foreign invaders, such as bacteria and viruses, that are bound to a human leukocyte antigen (HLA) molecule, according to the study.

The authors noted that individuals have a specific makeup of HLA molecules, and similarly to fingerprints, they are unique to each person. Therefore, finding individuals with the exact same receptor is extremely rare.

"The likelihood of finding the exact same T cell receptor in different individuals is extremely low, like winning the lottery, and is likely playing a role in the control of HIV," Carine Farenc, co-author of the study, said in the press release.

The researchers examined the binding of the super T cell receptor and an HIV antigen under the Australian Synchrotron, a football field-sized microscope.

They found that the killer CD4 T cells were able to recognize fragments of HIV in patients with different genetic makeups. They could also bind to the HLA molecules of 25% of the world population and potentially more as research advances, according to the study.

The authors noted that these findings could eventually lead to a new immunotherapy for patients with HIV.

Reference

Benati D, Chakrabarti LA, Ciacchi L, et al. CD4 T cell-mediated HLA class II cross-restriction in HIV controllers. Science Immunology. 2018; 3 (24): eaat0687 DOI: 10.1126/sciimmunol.aat0687