t cell

A discovery by Australian scientists could have implications for type 1 diabetes research following a study on T cell receptors (TCRs).

Prior to findings made by Monash University, the current assumption held by immunologists was that when TCRs bind to major histocompatibility complex (MHC), they “dock” in a fixed orientation, and can only function this way.

When this happens, a signal is conveyed to the immune system that a T cell is infected, and T cells launch an attack of the area.

A Monash team have contradicted this belief by demonstrating that TCRs can bind to immune molecules in a completely reversed order.

Impact on type 1 diabetes

These findings could change the way T cells are researched within type 1 diabetes, and how the autoimmune disease develops.

Earlier this year, British scientists identified a particular type of T cell – the follicular helper T – as being responsible for the immune attack that characterises type 1 diabetes. This T cell leads to insulin-producing cells being destroyed and the body can no longer produce insulin, which is responsible for regulating blood sugar levels.

The Monash researchers had been investigating TCRs associated with a regulatory T cell (Treg), also known as a peacekeeping cell, which preserves insulin-producing cells from immune attack.

“In type 1 diabetes there are not enough of these peacekeeping {Treg} cells and so the immune system continues to attack and destroy insulin-secreting cells,” explained co-author Dr. Hugh Reid.

Using a fragment of insulin protein and an MHC molecule, the researchers stimulated production of Treg cells. This was done using a reversed mode of connection, and in spite of this, the cells still suppressed the attacking response of the immune system in the presence of insulin.

The researchers suggest that all types of T cell could connect with MHC in different orders, challenging established views of scientists and opening up possible research opportunities.

Reid added: “We will now set out to determine more TCR-MHC interactions of the same regulatory T cell subset and compare them to the other T cell TCR-MHC interactions derived from the inflammatory T cells.”