For Quick Alerts
ALLOW NOTIFICATIONS  
For Daily Alerts
Oneindia App Download

Why some people with HIV develop AIDS and others don't

By teronpi
|
Google Oneindia News

London, May 6 (ANI): Scientists are a step closer to understanding why some people with HIV develop full-blown AIDS, and others don't.

Researchers in Massachusetts and California say that the answer lies in how the immune cells that recognize invaders are educated a finding that may pave the way for new strategies for designing an HIV vaccine.

The human immune system detects foreign cells with the help of cell-surface proteins called human leukocyte antigens (HLAs). Each person's cells carry a particular set of HLA molecules - the person's HLA type - which bind fragments of virus or bacterial protein and 'present' them to T cells, the immune cells that recognize and attack infected cells.

But before T cells are ready to perform their killer function, they are in effect trained on fragments of the body's own proteins - self-peptides - in an organ called the thymus.

To 'graduate' from the thymus, a T cell must be able to recognize at least one combination of HLA molecule and self-peptide, which provides the template for its subsequent immune response against a foreign peptide bound to that HLA molecule. T cells that bind to self-peptides very strongly, however, are rejected, as they would attack the body's own cells.

Researchers began with two observations. First, HIV-infected people who manage to keep the virus in check - so-called 'elite controllers' - often carry a particular HLA gene variant, HLA B571. Second, people with this gene also have a higher risk of developing autoimmune diseases, in which the immune system does produce a harmful response against the body's own proteins.

Arup Chakraborty, an immunologist at the Massachusetts Institute of Technology in Cambridge, and one of the lead authors of the study, thought the two observations might be related.

He had not previously studied HIV, but he had studied how T cells are selected in the thymus by their ability to recognize specific HLA molecules and the peptides bound to them. He surmised that the HLA molecules of elite controllers might be binding a relatively small number of self-peptides.

Indeed, a look through a database of the binding properties of HLA molecules revealed that HLA B57, along with HLA B27 - which also protects against HIV - binds a much smaller proportion of self-peptides than HLAs that are not protective. The researchers then used a computer algorithm to predict how this would affect T-cell maturation.

T cells that develop in people with the HLA B57 gene would be presented with a smaller variety of peptides in the thymus. Their model showed these cells have broader activity and would be likely to recognize HIV even if the virus mutates, allowing the immune system of elite controllers to keep the infection under control.

But that same property would also make them more likely to turn on the body's own cells, explaining why HLA B57 leads to a higher risk of developing autoimmune diseases. "If you have a smaller diversity of self-peptides in the thymus," says Chakraborty, "there's a higher probability that T cells with a stronger reactivity and cross-reactivity" might be released.

Testing their model on data from 1,900 HIV-infected individuals with known HLA types, 1,100 of which were elite controllers, the researchers found that the progression of the disease was strongly correlated with the number of self-peptides an HLA molecule was able to bind.

The study has been published online in Nature. (ANI)

For Daily Alerts
Get Instant News Updates
Enable
x
Notification Settings X
Time Settings
Done
Clear Notification X
Do you want to clear all the notifications from your inbox?
Settings X
X