Math explains HIV immunity

A mathematical model has revealed part of the secret to why some people linkurl:infected with HIV never get sick,;http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08997.html providing a new target in the attempt to harness that ability in a vaccine, according to research published in __Nature.__ HIV particles (green) budding from a lymphocyte.Image: C. Goldsmith, CDC People who can control their HIV infections carry a specific subtype of the gene for the major histocompatability co

HIV particles (green) budding
from a lymphocyte.
Image: C. Goldsmith, CDC

People who can control their HIV infections carry a specific subtype of the gene for the major histocompatability complex (called HLA in humans). The immune system relies on HLA molecules to train T cells to avoid attacking the body's own tissues by presenting self-peptides. T cells that don't bind too strongly to the HLA-self-peptide complex are then activated against pathogens. Researchers found that individuals with a specific subtype of the HLA molecule, HLA-B57, have a lower level of HIV RNA without any retroviral therapy -- but just how this molecule confers protection has been an area of intense study. Rather than attack the question with biochemistry and molecular biology, linkurl:Arup Chakraborty;http://web.mit.edu/akcgroup/ from MIT and his colleagues went after the question using mathematical models, which, according to Chakraborty, are well suited for investigating complex evolving systems like the immune system. (Read more about Chakraborty's take on using linkurl:physical sciences to understand immunology;http://www.the-scientist.com/2010/3/1/40/1/ in his March 2010 feature.) Chakraborty and his colleagues used their model to predict that the HLA-B57 subtype can bind to fewer self-peptides than other subtypes. As a result, this subtype trains T cells against fewer self-peptides. When that training is less restrictive (with fewer peptides presented), T cells leave the thymus with the ability to bind to a broader array of antigens than when their training is more restrictive. This makes their binding specific, but at the same time more flexible to variants of their target -- a crucial ability, given HIV's rapid rate of mutation. The researchers tested their model against samples taken from HIV patients, and found that, in those that tended to progress in their disease, their HLAs were also able to bind to more self-peptides. "This is a remarkable paper because it starts from a clinical observation, integrates it with experimental observations, generates a valuable model and derives from the model a deep understanding of the behavior of the human immune system. Rarely does one read a paper that stretches the mind so surprisingly far," said David Baltimore, in an MIT press release. While these findings might help target scientists' efforts in the search for a vaccine, they are a long way off from an immediate impact, Chakraborty warned. "We are in the early stages in HIV research," Chakraborty told __The Scientist.__ "We don't know for sure what it is about an immune response that might help it control HIV" infection and spread, he added. The study, said Chakraborty, implies that new vaccine efforts should try to find ways to mobilize and multiply T cells that are not only specific for the HIV virus, but that are also highly flexible in their binding -- a goal that scientists have not yet figured out how to tackle.
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