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, he said.

The team demonstrated that LAG-3 is cleaved by two metalloprotease enzymes, called ADAM10 and ADAM17. The activity of these enzymes is under controlled by distinct but overlapping signals generated from the T cell receptor, a specialized protein that allows T lymphocytes to “see” the outside world. In either case, when metalloproteases remove LAG-3, the brakes are taken off T cell activity. 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 other authors of the paper include Nianyu Li (formerly at St. Jude; now at Amgen Inc., Seattle), Yao Wang, Karen Forbes, Kate Vignali and Creg J. Workman (St. Jude); Bret S. Heale and John J. Rossi (Beckman Research Institute of the City of Hope, Duarte, Calif.); Paul Saftig (Christian- Albrechts University, Kiel, Germany); Dieter Hartmann (Leuven and Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium); Roy Black (Amgen Inc., Seattle); Carl P. Blobel (Weill Medical College of Cornell University, New York); and Peter J. Dempsey (University of Washington, Seattle).

This work was supported in part by the National Institutes of Health, a Cancer Center Support CORE grant, ALSAC and the German Research Foundation.

St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit www.stjude.org.

Related Health News:

1. Leukemic Cells Find Safe Haven in Bone Marrow The cancer drug asparaginase fails to help cure some children with acute lymphoblastic leukemia (ALL) because molecules released by certain cells in the bone marrow...
2. Chemical Found In Curry May Help Immune System Clear Amyloid Plaques Found In Alzheimer’s Disease UCLA/VA researchers found that curcumin -- a chemical found in curry and turmeric -- may help the immune system clear the brain of amyloid beta,...
3. Study of Leukemia Survivors Gives Info for Better Care Results from the longest follow-up study ever done of childhood acute lymphoblastic leukemia (ALL) survivors show the importance of long-term monitoring of former patients to...
4. Cord Blood America Marks 10th Anniversary of First in Nation Cord Blood Banking Services Between CorCell and Independence Blue Cross Cord Blood America, Inc. (BULLETIN BOARD: CBAI) , the umbilical cord blood stem cell preservation company (http://www.cordblood-america.com/ ) focused on bringing the life saving potential...
5. Data Presented at AACR Meeting Further Support The Advance of Semafore’s Targeted PI3K Inhibitor Into Phase I Trials Semafore Pharmaceuticals, Inc., an emerging leader in small molecule cancer therapeutics addressing critical cell signaling pathways, today announced that preclinical data presented at the 97th...