Bio-Chem. Researchers Develop New Treatment

By creating a three-dimensional picture of a protein interaction in the immune system, researchers in the biochemistry department have taken a step toward developing new treatments for autoimmune diseases.

In a collaborative effort, research teams under Biochemistry and Biophysics Professor Don C. Wiley and Higgins Professor of Biochemistry Jack L. Strominger, have provided new insight into how an immune response is triggered.

Their findings appear in today's issue of the science journal, Nature.

The scientists studied HLA-DRI, a protein which triggers immune responses by binding to foreign molecules and delivering them to T cells designed to attack invaders.

"Understanding the system is key to understanding autoimmune diseases," Strominger said.

He added that the research could lead to the development of vaccines or drugs for diseases including multiple sclerosis, diabetes and rheumatoid arthritis, all of which are caused by the malfunctioning of the immune system.

The researchers determined how the protein interacts with invader molecules using X-ray crystallography, a technique which elucidates the precise structures of molecules.

Charles A. Janeway, a professor of immunobiology at Yale University, acclaimed the researchers' efforts in an interview yesterday.

"I think that the main significance is that it allows us to understand clearly and visually how the immune system works," Janeway said.

The HLA antigen functions by binding to a fragment of a foreign molecule--in the study, a fragment of the flu virus--and alerting nearby T cells of its presence.

Today's article reported precisely how much of the protein bound to the flu virus and how much was left unbound to signal T cells.

"The importance is in seeing how peptide is bound to protein," said Lawrence. J. Stern, a post-doctoral student in Wiley's lab who was the primary author of the paper.

Wiley's and Strominger's teams began collaborating in the early '80s. In 1987, their combined efforts determined the structure of a similar protein-peptide complex.

Janeway said these earlier findings were the true breakthrough, and that today's research is a further development of the previous work.

"[Wiley's and Strominger's] work has really revolutionized how people talk and think about the immune system," he said.

Although today's findings will not necessarily surprise scientists, Janeway said, their importance should not be underestimated by the general public.

"These are only the details," he said. "But the details are important."

Both Janeway and Stern said the research is important for moving on to the next step in understanding immune responses, which involves studying how the complex interacts with the body's T cells.