Professor Andy Sewell 2_1 (2)

Seen for first time: T-cells knock out insulin

CARDIFF (UK) — T-cells in the human body, which help protect us from disease, can inadvertently destroy cells that produce insulin, new research shows.

Published in the journal Nature Immunology, the study may clarify the role of T-cells in the development of Type 1 diabetes.

Researchers isolated a T-cell from a patient with Type 1 diabetes to view a unique molecular interaction that results in the killing of insulin-producing cells in the pancreas.

“Type 1 diabetes is a result of the body’s own immune system attacking and destroying the cells in the pancreas that manufacture the hormone insulin. Insulin controls blood sugar levels and a lack of insulin is fatal if untreated,” says Andy Sewell, an expert in human T-cells at Cardiff University.

“The mechanism by which the body attacks its own insulin-producing cells in the pancreas is not fully understood. Our findings show how killer T-cells might play an important role in autoimmune diseases like diabetes and we’ve secured the first ever glimpse of the mechanism by which killer T-cells can attack our own body cells to cause disease,” he adds.

Co-author Mark Peakman professor at King’s College London says: “This first sight of how killer T-cells make contact with the cells that make insulin is very enlightening, and increases our understanding of how Type 1 diabetes may arise.

“This knowledge will be used in the future to help us predict who might get the disease and also to develop new approaches to prevent it. Our aim is to catch the disease early before too many insulin-producing cells have been damaged.”

The team hopes that by gaining a better understanding of this process it will put them in a much stronger position to devise new ways to prevent or even halt the disease.

“The results of Dr Sewell’s work provide key novel insights into T1D pathogenesis” says Teodora Staeva, director of Juvenile Diabetes Research Foundation Immune Therapies Program.

This unusual binding is thought to allow the T-cell to survive the culling process designed to rid the body of autoreactive T-cells. The structure of the killer T-cell receptor bound to the insulin peptide shows that the interaction is highly focused on just a small part of the molecule.

In a further study published in the Journal of Biological Chemistry, the same Cardiff and King’s team has shown that this focused binding mode allows this T-cell receptor to respond to over 1.3 million other peptides of different molecular shape.

This ability to bind peptides with a multitude of different shapes may provide a clue as to how autoimmune diseases are initiated.

It’s possible that this T-cell was raised to fight an infection via one of the other 1.3 million peptides it can recognize but then inadvertently also recognized insulin once it had been put on “red alert” by this infection.

The study was funded by the UK Biotechnology, the Biological Sciences Research Council, and the Juvenile Diabetes Research.

More news from Cardiff University: www.cardiff.ac.uk/news/

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