Monash researchers make fundamental advance in understanding T cell immunity

Full article issued by Monash University.

Researchers at Monash University supported by a Discovery Projects grant have provided a fundamental advance regarding how T cells become activated when encountering pathogens such as viruses.

The study was co-led by ARC Future Fellow Professor Nicole La Gruta, Australian Laureate Fellow Professor Jamie Rossjohn and former Future Fellow Professor Stephanie Gras, with first author Dr Pirooz Zareie from the Monash Biomedicine Discovery Institute.

The researchers have found that T Cells, which play a crucial role in the body's immune system, need to recognise pathogens such as viruses in a particular orientation in order to become activated to fight the intruder.

This activation occurs when special T cell receptors (TCR) on the surface of the T cell recognise and bind to the virus fragments (antigens) on infected cells. After recognising the antigen, the T cell activates and is able to kill the infected cell.

'The central issue is that there are millions of different T cell receptors (TCRs) in the human body, and a vast array of viruses, making it difficult to understand the rules around how T cell receptor recognition of a virus drives T cell activation. Indeed, it is a problem that has remained contentious for over 25 years,' says Professor La Gruta.

'Our study has shown that the orientation in which the T cell receptor binds is a primary factor determining whether the T cell receives an activating signal.'

'This is an advance in our fundamental understanding of how a T cell needs to ‘see’ pathogenic antigens in order to be activated,' she said. 'It has clarified a critical mechanism essential for effective T cell immunity. It is also relevant to the ongoing development of immunotherapies that aim to boost the activation of T cells.'

 

TCR-pMHC recognition – through the looking glass. The image shows a brightly coloured canonical interaction between TCR and pMHC which is conducive to signal transduction. The faded mirror image shows a reversed TCR-pMHC interaction which is unable to support signal transduction and thus T cell activation. Image created by Dr. Erica Tandori (Rossjohn lab)