A tiny minority of people, about one in 300, can keep HIV from progressing to AIDS without drugs. In such "elite controllers," the virus is kept in check with "killer" cytotoxic T lymphocyte cells, earlier research has shown. In a new study, investigators found that elite controllers differ from others with HIV in how well these killer cells work, not in how many cells they have. In particular, the effective strain has receptors that are better able to identify HIV-infected white blood cells for attack.
People with HIV "have tons of these killer cells," said Bruce Walker, an infectious-diseases expert at the Ragon Institute in Massachusetts. "We have been scratching our heads since then, asking how, with so many killer cells around, people are getting AIDS. It turns out there is a special quality that makes [some cells] better at killing."
Walker and colleagues examined 10 people with HIV: five who took antiretroviral therapy to control the virus, and five elite controllers who were naturally healthy.
"What we found was that the way the killer cells are able to see infected cells and engage them was different," Walker said. "It is not just that you need a killer cell, what you need is a killer cell with a [T cell] receptor that is particularly good at recognizing the infected cell. This gives us a way to understand what it is that makes a really good killer cell."
Generating such cells, however, remains problematic for researchers. "The next step is to determine what it is about those receptors that is endowing them with that ability," said Walker. "Each secret that HIV reveals is putting us in a better position to ultimately make a vaccine to control the virus."
[PNU editor's note: The study, "TCR Clonotypes Modulate the Protective Effect of HLA Class I Molecules in HIV-1 Infection," was published in Nature Immunology (2012;doi:10.1038/ni.2342).]
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