Type 1 diabetes research breakthrough as Australian researchers challenge T cell immunology

A breakthrough by Australian researchers could change the way T cell receptors (TCRs) are studied, and have implications for type 1 diabetes.
A team at Monash University have demonstrated for the first time that TCRs can bind to immune molecules known as the major histocompatibility complex (MHC) in a completely reversed orientation.
When TCRs bind to MHC, this signals that a T cell is infected and T cells launch an attack of the area reported as being infected.
This finding contradicts the current assumption held by scientists that TCRs must bind to MHC in a specific orientation to create a signal to the immune system.
Type 1 diabetes and T cells
Earlier this year, British scientists identified a particular type of T cell – the follicular helper T cell – that triggers an immune response which leads to type 1 diabetes. This T cell results in the destruction of insulin-producing cells, and the body cannot produce insulin, which is responsible for regulating blood glucose levels.
This new discovery about the way immune cells work could result in forthcoming studies aimed at identifying how the immune system attacks insulin-producing beta cells, which characterises type 1 diabetes.
Monash researchers had been investigating TCRs associated with a regulatory T cell (Treg), which prevents the body from attacking its own insulin-producing cells.
Co-author Dr. Hugh Reid, Monash University, explained: “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.”
Immunologists have long believed that TCRs only function when they interact with MHC in a “fixed” way, and that for T cells to be activated, they must “dock” in this fashion.
Using a fragment of insulin protein and an MHC molecule, production of Treg cells was stimulated, and despite a reversed mode of connectio, the cells still suppressed the attacking immune response in the presence of insulin.
By suggesting that all types of T cells could connect with MHC in a different order, the researchers have challenged established views and opened up further research opportunities.
“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,” added Reid.