28 Apr 2020
Day of Immunology: Finding your MAITS
To celebrate Day of Immunology on 29 April 2020, we asked some of our scientists to summarise their research advances into the immune system. Each day this week we’ll be delving into a different area of this research. In today’s article we explore MAIT cells, our immune system’s internal defence that stands guard against infection.
If you could dive into the body and travel along it’s many passages and cavities you would find that they’re lined with membranes rich in mucous: the mucosa. The mucosa lines the respiratory, urinary and digestive tracts, which are the first ports of call for bacteria entering the body. But these areas also harbour their own security team - the mucosal-associated invariant T (MAIT) cells. MAIT cells are specialised immune cells found in these areas, as well as in the blood and liver, and defend the body against infection. They detect infection by recognising the presence of vitamin B metabolites, small molecules made by bacteria as part of their metabolism, and attack or raise the alarm for additional MAIT support.
We still have much to learn about these cells and their important role within the immune system. Recent work from researchers in Professor Jim McCluskey’s Laboratory at the Doherty Institute used a protein called MR1 to detect and study MAIT cells in humans and mice. The MR1 captures vitamin B2 (riboflavin) or vitamin B9 (folic acid) metabolites to be detected by MAIT cells with a specialised receptor. The team created “MR1 tetramers”, which consist of four MR1 molecules together, thereby increasing the chance that at least one will bind to the MAIT cells. These tetramers are labelled with a fluorescent tag that can subsequently be detected to pull out the MAIT cells they have bound. Tetramers have become an invaluable tool to study these cells, leading to a rapid increase in understanding of MAIT cell biology.
In a study led by Dr Zhenjun Chen, researchers have studied the response of lung MAIT cells following infection of mice with bacteria such as Legionella longbeachae or Salmonella enterica Typhimurium, which cause Legionnaires’ disease and gut inflammation respectively. These infections cause an expansion of MAIT cell numbers, making them more easily trackable with tetramers and providing a larger pool of cells to be used in further studies.
MR1 tetramers can also be used to determine the number and function of MAIT cells in human blood samples. Once MAIT cells become activated by recognising MR1 and bacterial vitamin B metabolites, they produce a large number of molecules that call on other immune cells. By learning what kind of molecules MAIT cells produce when activated, the researchers can gain insight into how MAIT cells influence the rest of the immune system and attack infectious bacteria.
MAIT cells are abundant and fast acting compared to other immune cells, making them an attractive target for immunotherapies. Learning more about MAIT cells will guide the development of therapeutics that harness their functions and abilities within the body.
Two papers have been published on this research in Current Protocols Immunology: Characterization of Human Mucosal-associated Invariant T (MAIT) Cells and Characterization and Purification of Mouse Mucosal-associated Invariant T (MAIT) Cells