Science in Medicine: Seeing structure of immune response

Dr. Ian A. Wilson

Few treasure hunters would recognize this crystal if they saw it. It wasn't extracted from a mine, and it will never be displayed in a museum. This crystal is a diamond of our immune system and Dr. Ian A. Wilson knows it very well.

A molecular biologist at the Scripps Research Institute in La Jolla, Calif., Wilson led a team of researchers in 1996 who determined the three-dimensional crystal structure of the primary recognition event between T cells and other cells.

"The main goal of our research program is to understand macromolecular recognition, especially such events in the immune system," says Wilson.

Imagine T cells, the warriors of the immune system, roaming our bodies seeking out foreign invaders. They are constantly scanning the surfaces of cells. If certain T cells detects abnormalities, they will release enzymes to destroy the cell and then float away in search of another fight, while other T cells, helper T cells, will help produce anitbodies to ward off invaders, Wilson said.

The primary interaction, or recognition event, takes place between the T cell receptor (TCR) and peptide complexes on the surfaces of all nucleated cells. As the two cells momentarily bind, the TCR determines whether or not the other cell is dangerous by the structure of the peptides on its surface. When a virus infects a cell, for instance, changes occur on the cell surface; thus, the structural interaction with the TCR is different, causing the killer T cell to release its enzymes.

Now, imagine literally freezing these interactions. Using cryogenic technology to freeze the molecule and X-ray technology to map its shape, Wilson and his colleagues were able to determine the fundamental structure of this recognition event.

Knowing the structure will allow researchers to develop drugs that will help boost our T cells in their battles against microorganisms they don't normally beat, such as cancer cells, or the HIV virus.

Wilson will discuss these possibilities, as well as other topics, in a lecture, titled "Structural Basis of Immune Response and Cytokine Receptor Activation," from 3 to 4 p.m. on Friday, April 17, in room T-625 of the Health Sciences Center. Wilson, this year's annual lecturer in the Science in Medicine series, will also discuss research aimed at developing an oral alternative to the drug erythopoietin (EPO).

EPO is a hormone produced in the kidneys that stimulates the growth of red blood cells. For certain people with liver damage or anemia, production of EPO is down, and injections of the hormone are used to stimulate the growth of blood cells.

EPO is one of the most successful biotechnology products on the market. Wilson and his colleagues identified a small peptide mimetic that stimulates EPO cells, which in turn stimulate our bone marrow and cause the proliferation of red blood cells.

"This was a pretty stirring discovery in the biotech industry," Wilson says. "The mimetic is one-tenth the size of EPO and can carry out the same activity."

Wilson and his colleagues used the same X-ray crystallography techniques to determine the structure of the interaction between the mimetic and EPO cells. For this research, they recently won the Newcomb Cleveland Prize for the best paper in Science magazine.

"It provides us with leads for designing drugs that can have a major medical impact," Wilson said.

Wilson received a B.S. in biochemistry from the University of Edinburgh, Scotland, in 1971 and a Ph.D. in molecular biophysics from Oxford University in 1976.

Since 1987, Wilson has been chairman of the Structure and Chemistry Affinity Group, and a professor and lecturer in the Scripps Research Institute Graduate School in Molecular and Cell Biology/Structure and Chemistry. In 1996, he became a professor in the Skaggs Institute for Chemical Biology. ¶

Will Morton