Chemists team with U. of Chicago to describe a catalyst in immune response
As part of a multidisciplinary team of scientists from around the world, a Brigham Young University professor and his graduate students have helped to discover a key to how the body regulates its immune response.
The finding has important implications in uncovering the roots of baffling autoimmune conditions like multiple sclerosis, lupus and rheumatoid arthritis. The work also sheds light on how the body responds to threats such as viruses, bacteria and cancer.
The study is published online Nov. 12 in "Science Express," the online version of America's premier scientific journal, "Science," which fast-tracks articles with important implications for human health. Studies initially published online appear in later print editions of the journal.
This research revolves around special cells called natural killer T cells, which act as switches in the body, determining whether to unleash an aggressive response such as inflammation, or instead initiating a ramping down of such responses.
"The problem has been that we didn't know what the key looks like that unlocks that switch," said Paul B. Savage, professor of chemistry and biochemistry at BYU.
The missing key is an antigen, which acts as a signal for the immune system, sending it into action. Most antigens studied to date have been small pieces of protein, but the antigen in this case is a glycolipid, made up of sugars and a fatty molecule. Scientists knew there was an antigen involved in activating natural killer T cells because they could observe its effects, but the team of scientists including Savage is the first to identify and describe it.
"Now we know what the real key is so now we can start asking where that key is made, how it's regulated, and that will allow us to understand how these responses are regulated," Savage said. "We can start to manipulate the natural killer T cells into doing what we want – treat disease."
In addition to digging deeper to understand the process, researchers can now create artificial versions of the antigen and test their ability to ramp the immune system up or down.
This antigen also plays another crucial role by "selecting" natural killer T cells for duty – without its presence, they don't survive. Autoimmune diseases like multiple sclerosis or rheumatoid arthritis are cases when the body attacks itself with an inflammatory response. This can be a result of a lack of natural killer T cells, which exist to regulate the immune response so that it protects the body without damaging it.
"We can come back to these people that don't have a lot of natural killer T cells and have autoimmune diseases, and it's possible they don't have enough of this antigen," Savage said.
Describing the antigen is a huge step toward understanding the complete chain of events involved in immune response. When Savage and his colleagues published a paper in "Science" last year that hinted at the identity of the key antigen, he called identifying it "the Holy Grail for us." Now armed with this knowledge, researchers are much closer to uncovering why some people develop conditions like multiple sclerosis and others don't.
Savage and two of his graduate students, Ning Yin and Ying Gao, are organic chemists who created artificial antigens for the research team.
"Scientifically, this is extremely exciting because there have been so many at major universities around the world who have been after this," Savage explained. "Because we've combined a team of organic chemists with immunologists, we've been able to figure it out."
The lead authors on the paper are Dapeng Zhou and Albert Bendelac at the University of Chicago. In addition to the BYU team, other coauthors are at the Scripps Research Institute, National Institutes of Health, Goteborg University in Sweden, the Chinese Academy of Sciences and the University of New Hampshire.
