By following the journey of a T cell receptor immediately after it is spurred into action, UNSW scientists, discover how recycling centres inside immune cells control immune reactions.

Activation of T cells is essential to mounting an effective immune response. So, these immune cells are exquisitely sensitive to signals from their microenvironment. Activation of T cells relies primarily on their main receptor, the T cell receptor.

Once triggered, T cell receptors are taken from the plasma membrane and inside the cell, and eventually, they are recycled back to the cell surface.

“This back and forth movement of receptors is required for T cells to get fully activated, presumably by making fresh receptors available for further rounds of activation,” says Dr Jérémie Rossy, who led the study.

Using fluorescent proteins that can light up on demand, Dr Rossy—and his team at the EMBL Australia Node in Single Molecule Science, in the UNSW School of Medical Sciences—uncovered mechanisms that control how T cells regulate the presence of the T cell receptor at their surface to fine-tune an immune response.

The team’s findings are published in the journal Nature Communications.

“When receptors are internalised, they are immediately incorporated into a dedicated network of intracellular compartments that make up the recycling centre inside T cells,” says Dr Rossy.

Membrane organising proteins – called flotillins –play a key role in orchestrating the recycling of T cell receptors.

Flotillins make the connection between the machinery that takes receptors up into intracellular compartments, and the processes recycling these same receptors back to the cell surface.

Flotillins play a decisive role in T cell activation by selecting which T cell receptors get another chance at being triggered. The more receptors at the surface of a T cell, the more sensitive they are to stimuli.

“The proof that recycling of the T cell receptor is crucial for T cell activation lies within the fact that T cells that don’t express flotillins are severely impaired in their response to activation,” says Dr Rossy.

Image: Fluorescently labelled proteins used to track the movement of T cell receptors on the surface of and inside an activated T cell