The immune system attack seems to be led by one of two specific enzymes chopping off a protein called LAG-3 from the immune cells, according to investigators at St. Jude Children's Research Hospital. They report that this is the first example of a protein, required for dampening T-cell activity, being controlled by getting chopped off at the T cell's surface.
The team demonstrated that LAG-3 is cleaved by two metalloprotease enzymes, called ADAM10 and ADAM17. The activity of these enzymes is controlled by distinct but overlapping signals generated from the T-cell receptor.
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, Dario Vignali, Ph.D., associate member of the St. Jude Department of Immunology notes.
This finding represents a new concept in how T cells are regulated, says Dr. Vignali, who is also senior author of the report published in the January 24 issue of The EMBO Journal. He believes the discovery could thus demonstrate an additional way in which these drugs work.