Y. scientists contribute to immune discovery

Brigham Young University scientists are on an international team that has figured out how the body regulates its immune response.

That may unlock doors to prevent or treat autoimmune illnesses like lupus, multiple sclerosis and rheumatoid arthritis. And it could help explain how the body rallies to fight invaders like viruses, bacteria and even cancer.

The discovery was being published today in Science Express, the online version of the journal Science, and will later appear in the print edition of the journal.

Their research found the "key" that controls natural killer T cells, "the regulatory cells in the immune system that help control the type of immune responses it can generate" such as inflammation, said Paul B. Savage, professor of chemistry and biochemistry at BYU. That response is also responsible for multiple sclerosis, rheumatoid arthritis, lupus and other autoimmune-generated illnesses.

The natural killer T cells recently debuted on the world stage as key immune system regulators. What this research adds is evidence of the identity of the specific key antigen that signals the immune response. And this antigen is different from most known antigens, which are typically small pieces of protein. This one is a glycolipid, comprised of sugar and fatty molecule. While scientists knew an antigen turned on the natural killer T cells because they could see what it did, Savage and his colleagues are the first to identify it.

That will allow them to study where the key is made, what regulates it and how the responses are controlled, he said. They hope to manipulate the natural killer T cells to treat disease.

They also plan to create an artificial form of the antigen to see if they can slow down or speed up immune system response.

The same antigen that "selects" natural killer T cells for duty also has to be present for the natural killer T cells to form, Savage said. Without it, they don't survive.

In autoimmune diseases, the body attacks itself, using inflammation. It can result from lack of natural killer T cells, which are supposed to moderate immune response to protect without damaging the body.

Savage believes people with autoimmune diseases may not have enough of the antigen. By knowing what the natural antigen looks like, "we can in the future design synthetic keys to switch" the response on and off, he said. "We've already done this to some extent."

Last year, Savage and his colleagues published a paper in Science that hinted at what the key antigen might be. Identifying it, he said, would be "the Holy Grail for us."

Savage and two graduate students, Ning Yin and Ying Gao, are organic chemists who made the artificial antigens for the research.

He said that many researchers all over the world have sought this antigen, but teaming organic chemists with immunologists made the discovery possible.

He's hopeful that resulting treatments won't be too far down the road. "A lot of the work's already been done. Things are moving forward pretty rapidly. In terms of stimulating inflammatory response, there are already things in clinical trials" against diseases like hepatitis. "For treatment of autoimmunity, animal models are very encouraging."

Much natural killer T cell research is occurring worldwide because the cells play such a strong role in immune system response. "They are an attractive means of influencing immune responses," Savage said. "They work at the headwaters all the way upstream. Instead of treating symptoms, they treat effects."

Lead authors are Dapeng Zhou and Albert Bendelac at the University of Chicago. Co-authors are the BYU team and researchers from the Scripps Research Institute, National Institutes of Health, Goteborg University in Sweden, the Chinese Academy of Sciences and the University of New Hampshire.

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