Navigation Links
Immune System Gears Up by Specific Enzymes

St. Jude study shows LAG-3 protein on activated T lymphocytes slows replication until // ADAM10 and ADAM17 enzymes cleave it off to allow these cells to reproduce rapidly.

The complex task of launching a well-organized, effective immune system attack on specific targets is thrown into high gear when either of two specific enzymes chop a protein called LAG-3 off the immune cells leading that battle, according to investigators at St. Jude Children's Research Hospital.

These cells, called T lymphocytes, are key to the body’s ability to fight off infections, tailoring the immune response so it focuses on specific targets. When activated, certain T lymphocytes called effector T cells reproduce, increasing their numbers and enhancing their ability to protect the body.

The St. Jude finding is important because it represents a new concept in how T cells are regulated, according to Dario Vignali, Ph.D., associate member of the St. Jude Department of Immunology. The study offers the first example of a protein that is required for dampening T cell activity being controlled by getting chopped off at the T cell’s surface.

Certain drugs that inhibit metalloproteases now under development as treatments for multiple sclerosis and arthritis appear to work by keeping T cells on a tight leash, Vignali noted. The new discovery could demonstrate an additional way in which these drugs work. Vignali is senior author of a report on this work that appears in the January 24 issue of The EMBO Journal.

The investigators performed their studies using animal cells that were genetically modified to carry LAG-3 on their surface; the researchers also used drugs that inhibit enzymes that chop off LAG-3. The team demonstrated that the two enzymes that cleave LAG-3 are controlled by of distinct but overlapping signals generated from the T cell receptor, a specialized protein that allows T lymphocytes to “see” the outside world. The investi gators showed that the T cell receptor generates a different, specific signal to control the activity of these metalloprotease enzymes, called ADAM10 and ADAM17.

Specifically, the team demonstrated that ADAM10 normally cleaves LAG-3 even before the T cells are activated. After the T cell receptor receives signals from the immune system, it causes the gene for ADAM10 to make much more of this enzyme, substantially increasing the rate of LAG-3 cleavage. However, ADAM17 is inactive until the T cell receptor triggers a molecule called protein kinase C theta to activate this enzyme. In either case, when metalloproteases remove LAG-3, the brakes are taken off T cell activity.

“Appropriate control of T cell expansion during an immune response is critical,” Vignali said. “We have uncovered a new paradigm in which specialized cell surface enzymes control this process by modulating the expression of a molecule, LAG-3, that acts as an immunological molecular brake. In turn, this process is controlled by the strength of the T cell receptor signal—the immunological ‘accelerator.’ So the more the T cell ‘accelerates,’ the more the ‘brake’ is released.”

The St. Jude team previously reported that regulatory T cells, which prevent effector T cells from running out of control and causing damage to the body, use LAG-3 to rein in these activated effector T cells.

The current study in EMBO extends that finding by showing that cleavage of LAG-3 proteins on the surface of T cells allows them to greatly increase their proliferation rate during such a battle. The team also showed that cleaved pieces of LAG-3 do not contribute to T cell control, but are rather “waste” products that are swept away later.



Source-Erekalert
SRI
'"/>




Related medicine news :

1. Immune cells halt round in space
2. Immune function could benefit from exercise
3. Reviving the Immune System
4. Wrestling found To Be Good for the Immune System
5. Immune Boost With LHRH To Help Cancer And Transplant Patients
6. Researchers Find Out The Cause Of Immune Attacks Behind Hearing Loss
7. Block Immune System Chemical For Treating Asthma
8. Immune Response Of Human Beings Can Be Re-energized
9. Weizmann Institute of Science says Immune Cells Could Help Maintain Brain Function
10. Antidepressant drugs interacts with Immune cells
11. Specific Immune Mechanism against DNA viruses
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:12/5/2016)... Diego, CA (PRWEB) , ... December 05, 2016 , ... ... seen and heard the dangers and downsides of patients who do not do their ... The field of cosmetic dermatology is in the midst of a renaissance and every ...
(Date:12/5/2016)... ... December 05, 2016 , ... ... Rejuvenation" at the 2016 Anti-Aging & Beauty Awards at The Aesthetic & ... & Anti-aging Medicine European Congress (AMEC) brings together the industry’s leading scientific ...
(Date:12/5/2016)... ... December 05, 2016 , ... A ... Patch® significantly improves the reproducibility and accuracy of placing precordial electrodes with little ... , Over the last 60 years, studies have shown that single electrode misplacement ...
(Date:12/4/2016)... ... 03, 2016 , ... The Lymphoma Research Foundation (LRF) – ... serving the lymphoma community through a comprehensive series of education programs, outreach initiatives ... New York City, with long-time partners The Paul Foundation, on November 10, 2016. ...
(Date:12/4/2016)... , ... December 03, 2016 , ... While James Earl ... serving as host for in a show called "Front Page". One of the forthcoming ... years, breast cancer rates have plummeted in large part due to early detection. Like ...
Breaking Medicine News(10 mins):
(Date:12/5/2016)... India , December 5, 2016 According ... by Treatment modalities (Chondrocyte Transplantation, Growth Factor Technology, Tissue Scaffolds, Cell-free ... published by MarketsandMarkets, the market is projected to reach USD 779.8 ... a CAGR of 13.5% during the forecast period of 2016 to ... ...
(Date:12/5/2016)... Sanovas, Inc., a life science asset holding company ... wholly owned subsidiary, Intubation Science, Inc., and its LightSpeed Intubation ... http://photos.prnewswire.com/prnh/20161202/445251LOGO   ... Sanovas, Inc. ... There are over 40 million Endotracheal Intubations performed annually ...
(Date:12/5/2016)... WOONSOCKET, R.I. , Dec. 5, 2016 /PRNewswire/ ... CVS ) Research Institute and the U.S. ... the Assistant Secretary for Preparedness and Response (ASPR), ... showed that automated pharmacy notifications encourage patients ... a forecasted natural disaster. The study also affirms ...
Breaking Medicine Technology: