A key step in the processing of HIV within cells appears to affect how efficiently 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 label infected cells 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 senior author Sylvie Le Gall, of the Ragon Institute and an HMS associate professor of medicine at MGH. “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 recognize HIV-infected cells through tiny bits of viral protein, called peptides, displayed on the cell surface. Researchers from Microsoft Research analyzed the biochemical features of 166 HIV peptides and identified particular structural patterns associated with either stability or instability. The researchers then showed that substituting a stability-associated structural motif for an instability motif significantly increased peptide stability.
“Efforts to develop T-cell-based vaccines need to focus on producing epitopes that elicit the most protective response,” says Le Gall. “Modulating peptide stability offers a unique way of regulating epitope presentation in favor of producing the most effective defense against HIV.”
Adapted from a Massachusetts General Hospital news release. For the full story, visit: http://www.massgeneral.org/about/pressrelease.aspx?id=1360
Massachusetts General Hospital is an affiliated teaching hospital of Harvard Medical School.
