T cells are immune cells that use surface proteins called T cell receptors to recognize and attack foreign substances.
Certain T cells, known as invariant natural killer T cells (iNKT cells), have receptors that are self-reactive: they recognize the body's own tissues. Although self-reactive cells can attack the body and cause autoimmune disease, it is not currently known why iNKT cells are self-reactive as a part of their normal behaviour. Part of the reason that these cells have been so elusive is that they are found very rarely in the body.
To address this issue, PM Cancer Centre Senior Scientist Dr. Naoto Hirano and his team of researchers devised an innovative two-step process to generate a large number of iNKT cells. First, the team isolated a region of the T cell receptor gene that is common to most iNKT cells, and inserted the region into regular T cells—partially turning them into iNKT cells. To complete the process, they used molecular 'baits' containing proteins similar to self-proteins to attract and expand the population of self-reactive iNKT cells.
Using this pool of generated iNKT cells, the researchers analyzed the protein sequence of iNKT cell receptors and identified three characteristics that are common to those that are highly self-reactive.
"We have developed a novel method that will enable more in-depth research on this elusive immune cell," says Dr. Hirano. "Moreover, we have identified features of the T cell receptor that provide new insights to the role of self-reactive iNKT cells in maintaining health."
This work was supported by the National Institutes of Health, the Ontario Institute for Cancer Research, The Princess Margaret Cancer Foundation, a Knudson Postdoctoral Fellowship and the Canadian Institutes of Health Research.
CDR3-β sequence motifs regulate autoreactivity of human invariant NKT cell receptors. Chamoto K, Guo T, Imataki O, Tanaka M, Nakatsugawa M, Ochi T, Yamashita Y, Saito AM, Saito TI, Butler MO, and Hirano N. Journal of Autoimmunity. 2015 Dec 31. [Pubmed abstract]