( t need to be matched as closely as poss...)Early-stage immune system control of HIV may depend on inherited factors

t need to be matched as closely as possible in organ transplants, with perfect matches only possible between identical twins. Some studies have found that HIV patients with particular versions of HLA may be better able to control viral levels, but the diversity of HLA molecules ?each person may have up to six different varieties of Class I proteins ?has made investigating the role of HLA type in HIV infection challenging.

The current study was designed to determine the contribution of both HLA Class I and the particular viral fragments displayed on those molecules to the activation of HIV-specific CD8 cells. The researchers analyzed blood samples from more than 100 people recently infected with HIV, first determining their specific HLA types by DNA analysis. Then they focused on 173 HIV protein fragments known to bind to those HLA types to see if particular peptides were more powerful in activating the HIV-specific CD8 response.

The researchers found that, for many varieties of HLA, only a few HIV protein fragments were responsible for the activation of CD8 T cells early in infection. In addition, the same HLA types that had been previously identified in people who stay healthy for a longer period of time after initial infection were associated with a more powerful early-stage HIV-specific CD8 activity.

"While we can't say this for sure right now, it is looking like both the HLA Class I molecule and the specific viral sequences being displayed contribute to the strength of immune response against primary HIV infection," says Altfeld. "In addition, the combination of Class I molecules that an individual expresses, something that is genetically determined, seems to have a significant impact on the specificity and strength of that response.

"Identifying the HIV epitopes [viral fragments] that are particularly good at priming an early T cell response may be important to vaccine design, and the impact of an individual's
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Source:Massachusetts General Hospital

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