Proteins team up to turn on T cells

From California Institute of Technology:

IMAGE: Researchers imaged cells to identify proteins that affect the expression of a genetic switch for T cells. On the right, T cells where the switch is activated glow in yellow…. view more

Credit: Caltech

The fates of various cells in our bodies–whether they become skin or another type of tissue, for example–are controlled by genetic switches. In a new study, Caltech scientists investigate the switch for T cells, which are immune cells produced in the thymus that destroy virus-infected cells and cancers. The researchers wanted to know how cells make the choice to become T cells.

“We already know which genetic switch directs cells to commit to becoming T cells, but we wanted to figure out what enables that switch to be turned on,” says Hao Yuan Kueh, a postdoctoral scholar at Caltech and lead author of a Nature Immunology report about the work, published on July 4.

The study found that a group of four proteins, specifically DNA-binding proteins known as transcription factors, work in a multi-tiered fashion to control the T-cell genetic switch in a series of steps. This was a surprise because transcription factors are widely assumed to work in a simultaneous, all-at-once fashion when collaborating to regulate genes.

The results may ultimately allow doctors to boost a person’s T-cell population. This has potential applications in fighting various diseases, including AIDS, which infects mature T cells.

“In the past, combinatorial gene regulation was thought to involve all the transcription factors being required at the same time,” says Kueh, who works in the lab of Ellen Rothenberg, Caltech’s Albert Billings Ruddock Professor of Biology. “This was particularly true in the case of the genetic switch for T-cell commitment, where it was thought that a quorum of the factors working …

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