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:2/24/2017)... ... February 24, 2017 , ... The International Association of Eating Disorders Professionals (iaedp) ... You See” body image mannequin art competition. Selected from 15 submissions from around the ... revealed at the 31st annual iaedp Symposium, March 22 – 26 in Las Vegas. ...
(Date:2/24/2017)... ... February 24, 2017 , ... Castle Farms, the celebrated ... Giveaway, with the winning couple announced on Feb. 14, 2017, on Facebook. The ... local vendors: A Matter of Taste, Ryan Rousseau Enterprises, A Touch of Spring ...
(Date:2/23/2017)... ... 23, 2017 , ... Rare Disease Report®, which is the ... Rare Disease Day events, hosted by the Rare Disease Legislative Advocates (RDLA) on ... weekly e-newsletter and quarterly publication, will be conducting interviews with patients and advocates ...
(Date:2/23/2017)... ... February 23, 2017 , ... ... for the National Institute for Health and Care Excellence (NICE) framework. ... the National Health Service (NHS) to search, order and purchase medical and healthcare-related ...
(Date:2/23/2017)... (PRWEB) , ... February 23, 2017 , ... ... Phoenix, announced today that it will soon begin franchising throughout the U.S. starting ... mission to help bring the practice of meditation mainstream. Current Meditation will be ...
Breaking Medicine News(10 mins):
(Date:2/24/2017)... YORK , Feb. 24, 2017 ... Monteverde & Associates PC , a boutique securities firm ... New York City , announces that a class ... Massachusetts  against Inotek Pharmaceuticals Corporation ... of the Company,s securities between July 23, 2015 and December ...
(Date:2/24/2017)... ITL Limited, ( ASX: ITD ), ... für das zum 31. Dezember 2016 endende Halbjahr ... vorlegen zu können. Eine vollständige Präsentation „Ergebnisse von ... Sie hier . Glanzpunkte ... 2015: 1,04 Millionen USD; +104 %) Gewinn je ...
(Date:2/24/2017)... YORK , Feb. 23, 2017  This report ... Thousand by the following Products: Intermediates, ... in the report include Pharmaceuticals, and Agrochemicals. The report ... Japan , Europe , and ... for the period 2015 through 2022. Also, a six-year ...
Breaking Medicine Technology: