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Step in breakdown of HIV proteins essential to recognition, destruction of infected cells
Date:5/9/2011

A key step in the processing of HIV within cells appears to affect how effectively the immune system's killer T cells can recognize and destroy infected cells. Researchers at the Ragon Institute of MGH, MIT and Harvard have found that as HIV proteins are broken down within cells, a process that should lead to labeling infected cell for destruction by CD8 T cells there is a great variability in the stability of resulting protein segments, variations that could significantly change how well cells are recognized by the immune system. Their report appears in the June Journal of Clinical Investigation.

"We have identified a novel mechanism by which HIV escapes recognition by virus-specific cytotoxic T cells, says Sylvie Le Gall, PhD, of the Ragon Institute, the paper's senior author. "This discovery may help us better understand the immune-system failure that characterizes HIV infection and provide information critical to the successful development of immune-system-based therapies."

CD8 T cells that have been programmed to target and destroy HIV-infected cells recognize those cells through tiny bits of viral protein, called peptides, displayed on the cell surface. Details of how HIV proteins are broken down into peptides and loaded onto the specialized molecules, called MHC Class I, that carry them to the cell surface are not well understood. Also unknown is whether particular HIV peptides are more effective than others in flagging cells for destruction.

Le Gall and her team first discovered that HIV peptides reduced to a length of 8 to 11 amino acids within infected cells varied greatly in their stability, with some breaking down further within seconds and others remaining unchanged for nearly an hour. Collaborators David Heckerman, MD, PhD, and Carl Kadie from Microsoft Research analyzed the biochemical features of 166 HIV peptides and identified particular structural patterns associated with either stability or instabi
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Contact: Sarah Dionne
smdionne@partners.org
617-726-6126
Massachusetts General Hospital
Source:Eurekalert

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