Fit to a T Cell

Artwork of an immune cell (left) displaying an MR1 molecule (top right) that is interacting with a gamma delta T cell receptor (bottom right)

Dr. Erica Tandori, artist-in-residence, Rossjohn Laboratory

The immune system’s T cells are major players in the constant battle against harmful bacteria, viruses, and cancers. T cells interact with other cells through receptors—lock-like projections on the surfaces of T cells that bind to specific molecular “keys,” or molecules of the major histocompatibility complex (MHC) displayed on the surfaces of helper immune cells. For two decades, scientists have thought they had the workings of T cells’ lock-and-key mechanism down pat—until a recent discovery of another way T cell receptors bind.

A team of researchers from several institutions in Australia examined a little-understood type of T cell receptor—a gamma delta receptor—which binds to MR1, an MHC-like protein, in multiple human tissue types—both healthy and diseased. They used high intensity X-rays to closely image these gamma delta-binding sites in 3D. T cell receptors were thought to bind only to the top portion of MHC and MHC-like molecules, but the images showed that gamma delta receptors bind to the underside of MR1.

“Our study shows that gamma delta T cell receptors can bind in a wholly different manner,” said the study’s co-lead author, Nicholas Gherardin, a postdoctoral fellow at the University of Melbourne. “We think it is likely that this reflects a far greater diversity in the different ways that gamma delta T cell receptors bind their target molecules.”

The discovery of this way that T cell receptors bind to targets could produce a better understanding of immune response and recognition, ultimately leading to new therapies against infection and cancer. “Manipulation of the T cell receptor pathway via modulation of MHC and MHC-like molecules is an attractive avenue for drug development,” said co-lead author Jérôme Le Nours of Monash University. “But to exploit this in full, a comprehensive understanding of the rules governing these interactions is required.” (Science)