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ProteoLipid Protein (PLP)
Implicated In Multiple Sclerosis

Trotter JL, Pelfrey CM, Trotter AL, Selvidge JA, Gushleff KC, Mohanakumar T, McFarland HF
Journal of NeuroImmunology 84(2), 172-178
Washington University School of Medicine, Neurology Dept., St. Louis, Mo, USA
PMID# 9628460; UI# 98290424
Abstract

Scientists have identified ProteoLipid Protein (PLP), which may trigger the Immune System's attack on Myelin. Thereby, causing Multiple Sclerosis (MS). They hope part of this protein will eventually be useful for therapy.

"For years, researchers have been looking for something in Myelin that is more visible to the Immune System in MS patients than in healthy people " such a component is likely to be central to the disease".

Says John L. Trotter, M.D., The Gordon R. and Thelma B. Coates Scholar and professor of Neurology at Washington Univ, School of Medicine in St. Louis. "This is the first report of such a substance."

For the past 40 years, scientists have focused on a Myelin component called Myelin Basic Protein (MBP), which causes Experimental Allergic EncephaloMyelitis (EAE) an MS-like disease when injected into animals.

But in the 1970s, Trotter became interested in another constituent called Myelin ProteoLipid Protein (PLP). It accounts for about half of the protein in Myelin and, when injected, also gives animals EAE, Trotter has shown.

The protein has been largely ignored, however, because it doesn't dissolve in water and therefore is hard to study.

In 1991, Trotter's group was the first to show that human White Blood Cells (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 the virus-infected cells. But in Multiple Sclerosis and other AutoImmune Disorders it is believed, T-Cells misidentify and attack normal tissue.

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 Peptides.

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 Neurological Disorders and Stroke supported this research.


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