T cell trigger found

A necessary part of T cell activation, critical for immune response, has been discovered by scientists from the La Jolla Institute for Allergy & Immunology.

Proteins called septins help open a molecular channel within T cells to allow calcium to enter the cells. The influx of calcium is essential to turn on the T cells’ disease-fighting powers. Turning them up could help fight cancer or infections.

Conversely, the discovery also points the way to possibly inhibiting T cell activity selectively, said Patrick Hogan, a La Jolla Institute researcher who along with colleague Anjana Rao were the paper’s senior authors. This could give rise to safer drugs to stop immune rejection of transplanted organs, he said.

The paper was published Sunday in Nature.

Septins are known as structural proteins, used in budding yeast and trapping bacteria, for example. Their role in T cell activation was an unexpected finding, Hogan said.

These proteins occur in many parts of cells, but they’re often difficult to detect without careful study, Hogan said.

Earlier research led by Hogan and Rao showed that the protein ORAI1 forms the calcium channel’s pore. The septins encircle the pore. Hogan said it appears that the septins help place ORAI1 and another called STIM into position so that the pore operates properly.

Since septins are so important, Hogan said they’re not a direct target of research for possible immune-modulating drugs. “We’re looking for some other part of the complex that forms with septins that we wouldn’t have had a clue is there until we started looking for it, because of the septins.”

As part of the study, the researchers knocked out genes to find those necessary for activating T cells. They found 887 genes that appeared to be involved. Some of the genes appear to have no other known function, Hogan said.

“Since they don’t have another assigned function, it could be that many of them function only in this pathway, and they would be better targets,” Hogan said. “It’s a matter of sifting through them and finding which ones have other general functions and which ones may participate only in calcium signalling, and ideally only in T-cells.”