Protein Implicated In Multiple...( e is hard to study. In 1991 T...)

In 1991, Trotter's group was the first to show that human white blood cells or lymphocytes recognize PLP. These cells normally recognize host cells that are infected with foreign proteins such as viral components. They then proliferate, generating more T cells that recognize and destroy virus-infected cells. But in multiple sclerosis and other autoimmune disorders, T cells misidentify and attack normal tissue, like soldiers attacking their own. 

In the current study, Trotter and colleagues isolated T cells from 12 MS patients. They cultured the cells and exposed them to short strings of amino acids or peptides. These peptides were identical to various parts of the PLP molecule. If the T cells recognized a particular peptide, they proliferated. In this way, the researchers were able to identify three peptides that were familiar to most of the T cells.

They then looked for T cells that recognized these peptides in blood samples from the 12 patients and from 12 people who did not have multiple sclerosis. They found that the T cell that recognized one of the peptides -- corresponding to amino acids 95 to 117 of PLP -- was at least four times more common in the patients' blood. "There also were enough of these T cells to cause disease," Trotter says.

In contrast, the immune cells of MS patients do not recognize myelin basic protein more frequently than those of people without MS.

The researchers now will isolate T cells that recognize the 95 to 117 peptide. Then they will modify the peptide so it binds to these cells without making them divide.

This peptide would be a promising drug candidate because, with their recognition sites blocked, the T cells that attack PLP might be unable to bind to and destroy myelin. Patients therefore might remain in remission. "We would like to perform a pilot study in five to six years," Trotter says.

A grant from the National Institute of Neurologic
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Contact: Linda Sage
sage@medicine.WUSTL.edu
314-286-0119
Washington University School of Medicine
13-May-1998