HIV Infected Cells Killed by Newly Discovered Super Receptor

Unique set of "super" receptors on immune cells that are capable of killing human immunodeficiency virus (HIV) across genetically diverse populations was discovered by a team of researchers in Paris. The study comes as a major breakthrough when researchers are still battling for a genuine therapy that can eradicate the HIV globally and genetically different population.

The study was conducted by 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. It is currently published in Science Immunology.

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HIV Progression

When a person gets infected by HIV, fighter cells of the protective immune system called CD4 T cells can get depleted and drop drastically in numbers. This, in turn, weakens the immune system and becomes instrumental in the progression of the disease to AIDS (acquired immune deficiency syndrome).

CD4 T cells act as “helper” cells to killer CD8 T cells that destroy infected cells.

AIDS is kept in check by anti-retroviral therapy (ART) in more than half of the people living with HIV globally. However, even with ART, the CD4 T cell numbers can remain low. This is not the case with certain rare individuals termed HIV controllers, who can control HIV infection.

Associate Professor Gras and her colleagues found that HIV controllers can retain CD4 T cells of a higher quality, which makes them detect and react to minute amounts of the virus. Their immune systems can spontaneously control HIV infection and protect them from AIDS progression making them good study candidates to examine their potential role in HIV infection.

The superior CD4 T cells turn themselves into killer cells in HIV controllers. The killer CD4 T cells are capable of recognizing very low amounts of HIV, thanks to the expression of "super" T cell receptors on their surface. The current study team has found identical receptors across multiple HIV controllers.

"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.

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Human Leukocyte Antigen (HLA)

The Human Leukocyte Antigen (HLA) system comprises of cellular proteins located on the surface of white blood cells and other tissues that can trigger an immune system response. Each person has a unique HLA complex, a specific combination of HLA molecules, which help the immune system recognize foreign invaders like bacteria or viruses.

The HLA system serves as recognition molecules and presents antigenic peptides (from foreign substances like viruses and bacteria) to the T-cell receptor (TCR) on T cells which the T cells recognize.

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Study Design and Results

The researchers studied fifteen HIV controllers who had been infected with HIV but have immune systems that protect them from AIDs progression.

Monash University researchers used a giant microscope effectively known as Australian Synchrotron to study the binding of this super T cell receptor in complex with the HIV antigen.

The killer CD4 T cells present in the HIV controllers were able to recognize HIV fragment in genetically diverse individuals (with different HLA molecules).

“We found that these killer CD4 T cells can bind with HLA molecules shared by a quarter of the world population, a figure that is likely to increase as studies progress”, according to Associate Professor Gras.

The “super” T receptors found in HIV controllers can be used for immunotherapy treatments, and the rare individuals could thus hold clues to the cure for the disease.

Human Immunodeficiency Virus (HIV)

HIV harms your immune system by destroying the white blood cells that fight infection and puts you at risk for other serious infections and certain cancers. An HIV infection could progress to acquired immunodeficiency syndrome (AIDS) which is the final stage of infection with HIV.

HIV can spread through unprotected sex with an infected person, by sharing drug needles or through contact with the blood of an infected person. Women can give it to their babies during pregnancy or childbirth.

HIV infection can be detected through a blood test. As of now, there is no cure for the infection. However, identifying the disease early and treating it can increase a person’s lifespan.

Anti-retroviral therapy or ART to treat HIV/AIDS has turned a uniformly fatal disease into a manageable chronic condition for many. ART has to be initiated as soon as possible after diagnosis and taken daily to keep HIV under control, which benefits individual health and prevents HIV transmission to others.

According to a 2016 statistics report taken by the World Health Organization, 36.7 million people were living with HIV infection out of which 19.5 million people were receiving ART. While ART lowers the risk of mortality, it does not eradicate the virus. Around a million people died from AIDS in 2016.

Reference:

1. HIV/AIDS - (https://medlineplus.gov/hivaids.html)

Source-Medindia