Antigen receptor control of methionine metabolism in T cells

White blood cells known as T cells are an essential part of the immune system. If these cells do not work properly the immune system falls down, leading to disease and eventually death. T cells have receptors on their surface that can detect molecules that do not belong in the body and that may indicate an infection or cancer. When one of these foreign molecules is detected, the T cell will activate and transform to become better equipped to protect the body. These two processes known as activation and differentiation involve extensive changes within the T cell. Many of these changes rely on the addition of a small chemical tag onto molecules such as DNA, RNA or proteins. The tag, a methyl group, is most often obtained by breaking down a chemical called methionine, one of the building blocks of proteins. Like all other animals, humans cannot make methionine, and so we must instead obtain it through our diet or recycle it from existing proteins. This raised some questions: does the availability of methionine limit the activity of T cells? And, if so, is it the uptake or breakdown of methionine that has the biggest effect? Sinclair et al. answered these questions by studying T cells from mice. First, the T cells were activated, the proteins from those cells were then collected and quantified using a technique called high resolution mass spectrometry. In further experiments, the uptake and use of a radioactively labeled version of methionine was followed in activated T cells. Using these approaches, Sinclair et al. showed T cell activation increased the cells demand for methionine, and that T cells need a steady supply of methionine to remain activated. The main limiting factor in this process was the speed at which the cell could make the transport systems it needs to collect methionine from its surroundings. These findings could prove useful in developing treatments for diseases associated with uncontrollable T cells, such as leukaemia and certain autoimmune diseases. Such treatments could, for example, involve restricting the transport of methionine into T cells through drugs, or potentially via the diet.