Scripps Research Institute scientists have developed a new approach to identifying molecules that prevent T cells from attacking their host. They believe that this tool could aid the search for potential treatments for autoimmune diseases such as multiple sclerosis (MS) and blood cancers like myeloid leukemia.
The researchers arranged thousands of peptoids—molecules related to but more stable than the peptides that make up proteins—on a microscope slide so the pattern of binding antibodies and peptoids could be visualized. By looking at samples from animal models of a known disease like MS, peptoids that bind to antibodies closely associated with that disease could be recognized, according to the Scripps team.
The scientists also found that peptoids that bind to autoreactive T cells can be identified without knowledge of the specific antigen, providing an unbiased method with which to search for potentially useful compounds. The study titled “Isolation of Antagonists of Antigen-Specific Autoimmune T Cell Proliferation” was published in the November 25 issue of Chemistry & Biology.
Most autoimmune research has focused on finding the disease-causing antigens first, says Thomas Kodadek, Ph.D., a professor in the chemistry and cancer biology departments at Scripps Florida and one of the study authors. "With our process, it doesn't really matter what the antigen is. That was really the breakthrough. We're setting up a system that recognizes T-cell receptors that are very abundant in a sick animal and at low levels in a healthy animal.”
Molecules that target autoreactive T cells directly while ignoring those T cells that recognize foreign antigens could serve as the foundation for a novel drug development program. "Almost without exception, drugs currently used to treat autoimmune conditions either inhibit something downstream of the autoimmune response itself, like inflammation, or they moderate the immune system nonselectively, and that results in significant side effects," Dr. Kodadek says.
The new study, though, isn't the final answer, he asserts. The research used a model of MS triggered by a single antigen, but in humans there could be two or many antigens triggering such an autoimmune disease. The method may be more easily applied to blood cancers, though, since the disease-causing T cells have been fully characterized and there are very few of them, Dr. Kodadek notes.