News

Awarded May 2020 for a period of five years

Project

Targeting vitamin-reactive T cells for enhanced immunity

Context

T cells are significant immune cells that play a critical role in responding to harmful bacterial pathogens. Mucosal Associated Invariant T cells (MAIT cells) are an abundant T cell population, both in the blood stream and at mucosal sites, such as in the lungs and intestines, but there is much to learn about their role in immune function.

“Our team at the Doherty Institute, along with Australian and international collaborators, discovered over five years ago that MAIT cells detect immune invaders by recognising small vitamin B metabolite-based antigens captured and presented on the MHC Class I-related (MR1) molecule,” said Dr Alexandra Corbett.

The research team found that these antigens are produced as a by-product of vitamin B2 (riboflavin) biosynthesis, which is an essential metabolic pathway for many microbes, thus acting as a molecular signature for immune recognition of growing microbes. Subsequently, further research has shown that MAIT cells can provide an important contribution to immune protection against several bacterial infections.

MAIT cells provide a new opportunity for immune interventions such as boosting immune responses by vaccination. They can also play a detrimental role during chronic infection, so in some settings it may be beneficial to specifically block them.

“Research has shown that MAIT cells show great promise to offer immunological protection. However we don’t fully understand the range of vitamin-based antigens that MAIT cells can recognise, how these are produced in vivo by pathogenic or commensal microbes, and how the recognition of these molecules by MAIT cells drives their immune response.”

By addressing key questions around MAIT cell antigen production and recognition in different settings, the current research will pave the way for therapeutic manipulation of MAIT cells, with potential applications in infectious disease, autoimmunity and cancer.

“With the support of the NHMRC Investigator Grant and building on the strong foundation and tools we have developed, our team will gain detailed knowledge of MAIT cell antigen recognition, signals driving MAIT cell functions in various settings, and their capacity for protective or pathogenic immune responses. Ultimately, this research program will allow us to fine tune our understanding of MAIT cells and harness these important immune cells in vaccines or therapies,” Dr Corbett said.