Researchers Engineer A Way To Improve T-Cell Receptors

CHAMPAIGN, Ill. -- University of Illinois scientists have come up with a way to improve the properties of T-cell receptors -- and potentially other proteins. Their success opens the door to manipulating a virtually untapped portion of the immune system to fight a variety of autoimmune and viral diseases. In a biotechnological breakthrough, the researchers showed that mutations within two regions of the receptor protein allowed it to be displayed on the surface of yeast. The work appears in the May 11 issue of the Proceedings of the National Academy of Sciences.

The researchers used a yeast-display system, which was created earlier at the U. of I., in combination with directed evolution -- a genetic engineering process in which a protein is subjected to random amino-acid changes, and then only those proteins with desired properties are selected. Their selection process also involved the use of flow-cytometry equipment at the U. of I. Biotechnology Center.

"T-cells and their T-cell receptors represent one-half of the immune system's capability to recognize infection," said David M. Kranz, a professor of biochemistry. "There has not been a method available to engineer these like you can do with antibodies. This paper shows that we've found a way to begin engineering the recognition molecules from the T-cell immune system. Realistically, we're a long way from seeing new therapeutic approaches, but the development of this capability is a major initial step."

Such a strategy could prove beneficial in manipulating the immune system's ability to bind to infected cells, such as in the case of the AIDS virus or cancer where the infection often remains invisible to antibody-based treatments.

Likewise, the researchers said, genetically engineered receptors could be used to block inappropriate immune responses in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.

Scientists around the world have been refining a variety of mono

Contact: Jim Barlow, Life Sciences Editor
University of Illinois at Urbana-Champaign

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