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28 Nov 2016

NIH facility provides MR1 tetramers developed at Doherty Institute

Written by Dr Sidonia Eckle, Dr Alexandra Corbett and Professor Jim McCluskey.

A breakthrough Doherty Institute discovery has led to the generation of an analytical research tool for an immune cell type, Mucosal Associated Invariant T cells (MAIT cells). This tool, MR1 tetramer, is now being offered to researchers around the world by the National Institutes of Health (NIH, USA).

Using the physiological binding partner (or recognition element) of MAIT cells, termed MR1, MR1 tetramers can be used to unequivocally identify MAIT cells in the blood and tissues of humans and mice, previously not possible.

Whilst MAIT cells are highly abundant in the human body, consisting of up to 10 per cent of the T cells in the blood and even more abundant in organs such as the liver, our knowledge about this cell type is limited. The MR1 tetramer has opened up the path for researchers to study the role of MAIT cells in health and disease.

In collaboration with Professor Jamie Rossjohn (Monash University) and Professor David Fairlie (University of Queensland), MR1 tetramers were developed in University of Melbourne Professor Jim McCluskey’s laboratory at the Department of Microbiology and Immunology at the Doherty Institute following a landmark discovery.

In an interdisciplinary effort, the teams of Professor McCluskey, Professor Jamie Rossjohn and Professor David Fairlie revealed that T cells do not only have the capacity to respond to peptides and lipids but also to a third class of molecules, metabolites.

Namely, MAIT cells respond to a metabolite from the microbial vitamin B2 pathway(1, 2). Specifically a MAIT cell response is initiated when a receptor on the surface of MAIT cells binds to the vitamin B2 derived molecule attached to a protein called MR1.

Mimicking this event, a tetrameric version of MR1 with the vitamin B metabolite bound, MR1 tetramer, attaches to several surface receptors on MAIT cells. Having also a fluorochrome tag, MR1 tetramers effectively cause MAIT cells to light up in experimental set-ups such as fluorescent microscopy and analysis of cells in suspension called flow cytometry.

Being able to see MAIT cells and to distinguish MAIT cells from other immune cell types is the first step in delineating their function.

Professor McCluskey’s laboratory has provided the MR1 tetramers already to more than 40 laboratories in Australia, the USA and Europe at no cost. This also includes laboratories at the Doherty Institute where several aspects of MAIT cells are being addressed, including the role of MAIT cells in bacterial and viral infections, autoimmune and inflammatory conditions, MAIT cell ontogeny as well as antigen presentation. Ultimately a better understanding of MAIT cell function will allow harnessing these cells for immunotherapies.

Following the high demand from researchers to study MAIT cells a licensing deal of the patented technology is now in place with the NIH tetramer core facility that offers MR1 tetramers in 8 colours.


(1) Kjer-Nielsen L, …, Rossjohn J, McCluskey J. Nature 2012, 491:717-723.

(2) Corbett AJ, Eckle SB, Birkinshaw RW, Liu L, …, Fairlie DP, Kjer-Nielsen L, Rossjohn J, McCluskey J. Nature 2014, 509:361-365

Homepage image: Microscopy of human duodenum staining with MR1 tetramer. The white arrow indicates a MAIT cell and the yellow arrow a conventional T cell. Courtesy of Lyudmila Kostenko (Jim McCluskey’s laboratory).