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A new understanding of how immune system targets disease

y's lead author. "If confirmed, the findings could launch a new wing of research seeking to re-engineer viruses, bacteria and tumor cells to make them hundreds of times more likely to be noticed and destroyed by our immune system."

Study Details

As part of the immune response, T cells, one type of white blood cell, partner with dendritic cells to make careful decisions about which pieces of pathogens will trigger a full-scale immune attack. Dendritic cells roam the body, checking each particle they come across for a self or invader "label." Upon encountering an invader, a dendritic cell will "swallow it," cut it up, and carry the pieces to the nearest lymph node.

Once in the lymph node, major histocompatibility complex (Mhc) proteins inside the dendritic cell present immunodominant epitopes on the cell's surface for consideration by T cells gathered there. Once activated by high enough levels of target epitope for long enough periods of time, T cells become armed and capable of destroying the pathogen in question.

Sant's study provides the first proof that it is something about the invader epitope itself that drives and focuses T cell response, and not some action of enzymes inside the dendritic cell as once thought. The quality determining immunodominance is the strength and lifespan (kinetic stability) of the bond between the Mhc protein and a given epitope. Kinetic stability determines whether, in the face of competing reactions within the immune system, an epitope:Mhc complex can remain intact on the dendritic cell surface long enough to demand T cell attention. Sant's team found that immunodominant peptides were likely to stay bound to Mhc molecules for an average of 150 hours, where nondominant epitopes held on for less than 10 hours.

"What's exciting is that kinetic stability is determined by how tightly an epitope fits into the Mhc protein, and we can control that fit with standard techniques," Sant said. "By swit
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Contact: Greg Williams
greg_williams@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
26-Jul-2005


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