Artwork of a gamma delta T cell receptor interacting with MR1. Artwork by: Dr Erica Tandori, artist-in-residence, Monash BDI.
Original Published Date: 
Monday, December 23, 2019

Full article issued by the Monash University.

An ARC-supported team of scientists led by Monash University, the ARC Centre of Excellence in Advanced Molecular Imaging and the University of Melbourne at the Doherty Institute, have transformed our understanding of T cell recognition.

T cells represent a key component of our immune system, and play a critical role in protecting us against harmful pathogens like viruses and bacteria, and cancers. The more we understand about how they recognise, interact with and even kill infected or cancer cells, the closer we come to developing therapies and treatments for a range of conditions.

In order to interact with other cells in the body, T cells rely on specialised receptors known as T Cell Receptors (TCRs) that recognise virus or bacteria fragments that are bound to specialised molecules called major histocompatibility complex (MHC) or MHC-like. Over the past 20 years, the prevailing view was that TCRs sat atop the MHC and MHC-like molecules for recognition.

The team of scientists characterised a new population within a poorly understood class of T cells called gamma delta T Cells that can recognise an MHC-like molecule known as MR1. Using a high intensity X-ray beam at the Australian Synchrotron, the scientists obtained a detailed 3D image of the interplay between the gamma delta T cell receptor and MR1 revealing an intriguing result whereby the gamma delta T cell receptor bound underneath the MHC-like molecule for recognition. This highly unusual recognition mechanism reshapes our understanding of how TCRs can interact with their target molecules, and represents a major development in the field of T cell biology.

"Think of it like a flag attached to a cell. We always thought the T cells were coming along and reading that flag by sitting atop it. We have determined that instead, some T cells can approach and interact with it from underneath," said ARC Future Fellow, Dr Jérôme Le Nours from the Monash Biomedicine Discovery Institute, co-lead author on the paper.

"These are the types of fine and important details that can change how we approach future research avenues in T cell biology," said Dr Le Nours.

Photo credit: 

Artwork of a gamma delta T cell receptor interacting with MR1. Artwork by: Dr Erica Tandori, artist-in-residence, Monash BDI.