Navigation Links
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 instability. The researchers then showed that substituting a stability-associated structural motif for an instability motif significantly increased peptide stability, and vice-versa.

The stability of a peptide within the cell can significantly affect how much peptide is available to be loaded onto MHC Class I molecules and displayed on the cell surface. The authors found that several known HIV mutations significantly reduced peptide stability one common mutation virtually abolished the cell-killing action of CD8 T cells. The Microsoft team members have developed a model to predict the probable stability of specific HIV peptides, but more research is needed to determine how variations in stability affect the presentation of the peptide segments called epitopes to CD8 cells and whether changes in peptide stability lead to a more efficient immune response.

"Efforts to develop T-cell-based vaccines need to focus on producing epitopes that elicit the most protective response," says Le Gall, an assistant professor of Medicine at Harvard Medical School. "Modulating peptide stability offers a unique way of regulating epitope presentation in favor of producing the most effective defence against HIV."


'/>"/>

Contact: Sarah Dionne
smdionne@partners.org
617-726-6126
Massachusetts General Hospital
Source:Eurekalert

Related medicine news :

1. Discovery of relationship between proteins may impact development of cancer therapies
2. Pitt-Stanford research suggests aimless proteins crucial to disease
3. 2 proteins play key roles in Burkitts lymphoma
4. Scripps Research scientists develop powerful new methodology for stabilizing proteins
5. Communication pathways within proteins may yield new drug targets to stop superbugs
6. Scripps Research scientists identify first synthetic activator of 2 critical proteins
7. Scientists at IRB Barcelona and BSC publish the worlds largest video data bank of proteins
8. Misfolded neural proteins linked to autism disorders
9. Researchers find function of proteins that can enhance the progression of viruses and cancer cells
10. Hydrophobic proteins: Potential biomarkers for colorectal cancer
11. Expression of certain transporter proteins may predict resistance to drug therapy
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/5/2016)... IN (PRWEB) , ... May 05, 2016 , ... ... benefits advisory organization, announces McLaughlin & Smoak Benefits as the latest addition to ... Smoak Benefits has a dedicated team of compliance, wellness, human resources, and health ...
(Date:5/5/2016)... ... May 05, 2016 , ... Michael ... charity program created to assist the people of their local community. The agency ... organizations and community leaders. Their hope is to bring awareness to important local ...
(Date:5/5/2016)... ... May 05, 2016 , ... ... community enrichment program serving families of greater Dubuque, IA. The current campaign fundraises ... and honorably discharged veterans. Donations to Veteran’s Freedom Center may now be made ...
(Date:5/5/2016)... ... May 05, 2016 , ... TIME for Kids and The ZAC Foundation – ... partnership to reach nearly 1 million children with important water safety messages before summer ... leading cause of accidental death in children one to 6 years of age. ...
(Date:5/5/2016)... ... 05, 2016 , ... The 2016 Nike Soccer Camp will be directed by ... coaching staff. Together they bring their winning Vandals coaching philosophy to young athletes. Programs ... 5-13, and high school players. Session dates are as follows: , Youth Day Camp ...
Breaking Medicine News(10 mins):
(Date:5/5/2016)... May 5, 2016 ... addition of the  "Europe Thrombocythemia Market ...  report to their offering.  ... , ,The latest research Europe Thrombocythemia ... 2016, provides comprehensive insights into Thrombocythemia ...
(Date:5/5/2016)... , May 5, 2016 ... of the  "Europe Thalassaemia Market and Competitive ... offering.       (Logo: http://photos.prnewswire.com/prnh/20160330/349511LOGO ... Thalassaemia Market and Competitive Landscape Highlights - ... products, Thalassaemia epidemiology, Thalassaemia market valuations and ...
(Date:5/4/2016)... Westport, Conn., May 4, 2016  Compass Diversified Holdings ... the "Company"), an owner of leading middle market businesses, ... months ended March 31, 2016. First Quarter ... Distribution and Reinvestment ("CAD" or "Cash Flow") of $13.6 ... Reported net loss of $15.0 million for the first ...
Breaking Medicine Technology: