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Early-stage immune system control of HIV may depend on inherited factors

How well an individual's immune system controls HIV during the earliest phases of infection appears to depend on both the specific versions of key immune-system molecules called HLA Class I that have been inherited, as well as on the fragments of viral protein those molecules display to the T lymphocytes that usually destroy infected cells. In a report in the November issue of PLOS Medicine, researchers from the Partners AIDS Research Center at Massachusetts General Hospital (PARC/MGH) report that specific HLA Class I/HIV viral fragment combinations are associated with a more powerful antiviral response, findings that may help develop vaccines against HIV.

"We found that only a limited number of viral protein fragments from HIV-1 are targeted by the immune system in early infection and that the versions of HLA Class I previously associated with slower HIV-1 disease progression also contribute more to this initial antiviral immune response," says Marcus Altfeld, MD, PhD, of PARC/MGH, the paper's lead author.

An essential aspect of the immune response involves educating T cells to recognize pathogens or other "non-self" proteins. This is done by means of human leukocyte antigen (HLA) receptors that sit on the surface of virtually every cell. Immune system cells that ingest bacteria or parasites digest those pathogens and display protein fragments on their surface membranes via HLA Class II proteins. Virally infected cells display viral proteins on HLA Class I molecules, which activate the CD8 cytotoxic T lymphocytes that usually destroy infected cells. Although the CD8 response against HIV is ultimately ineffective in protecting infection, several studies have suggested that it plays a key role in determining how quickly the disease progresses after initial infection.

HLA ?also called major histocompatibility complex (MHC) ?proteins are also the primary markers of tissues as "self." Unique to each individual, these are the factors tha
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Source:Massachusetts General Hospital


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