A 'super' receptor that helps kill HIV infected cells

June 8, 2018, Monash University
CD4+ T cells, or helper T cells, in HIV controllers can interact with various HLA class II molecules presenting the same “piece” of HIV. These CD4+ T cells display cell-killing activity to suppress HIV. Credit: Vanette Tran

While treatments for HIV mean that the disease is no longer largely fatal, the world still lacks a true therapy that can eradicate the virus across a globally—and genetically different—population.

Monash researchers, together with colleagues from the Pasteur Institute in Paris, have discovered a unique set of "super" receptors on capable of killing HIV across genetically diverse populations, making them a potential candidate for immunotherapy treatments. The work was published today in Science Immunology.

Associate Professor Stephanie Gras and her team from Monash University's Biomedicine Discovery Institute (BDI) and ARC Centre of Advanced Molecular Imaging, and her colleagues from the Pasteur Institute in Paris, studied fifteen unique individuals who all had been infected with HIV (ANRS CO21 CODEX cohort), but have immune systems that protect them from AIDs progression. These rare individuals, called HIV controllers, could hold clues to the cure for the disease.

Upon HIV infection, CD4 T cells, which are an important part of our protective immune system, can be depleted and drop dramatically in numbers, leading to a weak immune system with the progression of the disease to AIDs. These CD4 T cells can remain low even when the disease is kept in check with anti-retroviral therapy (ART), which is currently provided to more than half of people living with HIV globally. ART lowers the risk of mortality but does not eradicate the virus.

Associate Professor Stephanie Gras at the Australian Synchrotron. Credit: Melissa Cowan

Associate Professor Gras and her colleagues found that HIV controllers are able to retain CD4 T cells of a higher quality, and are able to detect and react to minute amounts of virus, therefore representing a great opportunity to study their potential role in HIV infection.

"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. These killer CD4+ T cells could recognise 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," Associate Professor Gras said.

"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" Monash BDI's Dr. Carine Farenc, a co-lead author of the study said.

T cell receptors recognise virus or bacteria fragments bound to specialised molecule called Human Leukocyte Antigen (HLA). HLA molecules are like fingerprints: every person has a specific combination of HLA molecules, which help the immune system recognise foreign invaders like bacteria or viruses.

A 360° rotation of the TCR in HIV controllers attached to various HLAs. Credit: Stephanie Gras

Monash University researchers used the Australian Synchrotron, effectively a giant microscope the size of a football field, to study the binding of this super T cell receptor in complex with the HIV antigen. This revealed another remarkable feature of those killer CD4 T cells: their ability to recognise HIV fragment in genetically diverse individuals (with different HLA molecules).

The Gras team and their colleagues found that these killer CD4 T can bind with HLA molecules shared by a quarter of world population, a figure that is likely to increase as studies progress, according to Associate Professor Gras.

Statistics (from the World Health Organization):

In 2016:

  • there were 36.7 million people living with HIV
  • 1 million died from the disease
  • 19.5 million people living with HIV were receiving antiretroviral treatment (ART)

Explore further: Unraveling the mysteries of the natural killer within us

More information: M. Galperin el al., "CD4+ T cell mediated HLA class II cross-restriction in HIV controllers," Science Immunology (2018). immunology.sciencemag.org/look … 6/sciimmunol.aat0687

Related Stories

Unraveling the mysteries of the natural killer within us

October 24, 2011
Scientists have discovered more about the intricacies of the immune system in a breakthrough that may help combat viral infections such as HIV.

Researchers makes 'natural born killer' cell discovery

August 31, 2017
An unexpected role for a white blood cell called the Natural Killer (NK) cell - a critical cell for ridding the body of infection and cancer, has been discovered by researchers at New Zealand's University of Otago.

HIV: Identification of receptors in patients spontaneously controlling infection

May 18, 2016
A small number of patients infected by HIV spontaneously control viral replication without antiretroviral therapy, and do not develop the disease. The ability of these rare patients, known as "HIV controllers", to suppress ...

Scientists discover new way that HIV evades the immune system

April 17, 2018
Scientists have just discovered a new mechanism by which HIV evades the immune system, and which shows precisely how the virus avoids elimination. The new research shows that HIV targets and disables a pathway involving a ...

Big step towards cure for lifelong viral infections

August 3, 2016
New research has taken us a step closer to finding a cure for human immunodeficiency virus (HIV), as well as other infections including the glandular fever virus, which is associated with the development of lymphoma. Some ...

'Mix and match' assembly instructions guide immune cell attacks

September 5, 2017
Institute researchers have discovered how immune cells use a unique set of assembly instructions to 'mix and match' how they respond to, and kill, tumour and diseased cells.

Recommended for you

A bad influence—the interplay between tumor cells and immune cells

October 16, 2018
Research at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) yielded new insights into the environment surrounding different types of lung tumors, and described how these complex cell ecosystems may in turn ...

New immunotherapy targeting blood-clotting protein

October 15, 2018
Normally, the blood protein fibrin does not enter the brain. But in several neurological disorders, the blood-brain barrier—which keeps large molecules in the blood from entering the brain—becomes abnormally permeable, ...

Function of neutrophils during tumor progression unraveled

October 15, 2018
Researchers at The Wistar Institute have characterized the function of neutrophils, a type of white blood cells, during early stages of tumor progression, showing that they migrate from the bone marrow to distant sites and ...

Immune health maintained by meticulously ordered DNA

October 15, 2018
Walter and Eliza Hall Institute researchers have revealed how immune health is maintained by the exquisite organisation skills of a protein called Pax5.

Enzyme that triggers autoimmune responses from T-cells in patients with MS found

October 11, 2018
A team of researchers from Switzerland, the U.S. and Spain has isolated an enzyme that triggers an autoimmune response from T-cells in patients with MS. In their paper published in the journal Science Translational Medicine, ...

Scientists reveal new cystic fibrosis treatments work best in inflamed airways

October 11, 2018
A new UNC School of Medicine study shows that two cystic fibrosis (CF) drugs aimed at correcting the defected CFTR protein seem to be more effective when a patient's airway is inflamed. This is the first study to evaluate ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.