How ‘lipid rafts’ help us mount an immune response

Lewis Carroll might have dreamed up the ‘lipid rafts’ that float around inside our cell membranes. Yet far from featuring as a subplot in Through the Looking Glass, these tiny fat-enriched platforms appear to ramp up the sensitivity of certain immune cells, helping us mount an immune response.

So say Australian immunologists in new findings that advance our understanding of killer T cells, the immune cells that roam our bodies like a patrolling army looking for invaders.

Dr Jae-Ho Cho and Professor Jonathan Sprent from Sydney’s Garvan Institute of Medical Research have described the role of lipid rafts within the cascade of sub-microscopic events that help T cells survive and thrive in a paper now published online in Immunity.

T cells can survive for decades after being produced in the thymus, although they may not start responding to invaders for years. It has been known for some time that they depend on two signals for survival: contact with ‘self’ molecules through a cell surface receptor and contact with a growth factor known as interleukin 7, or IL-7.

“While the prevailing view has been that these are two quite distinct signals, we show that the ‘self’ signal makes the cells more sensitive to growth factors, in particular IL-7,” said Professor Sprent.

T cells continually bump into ‘self’ molecules as they roam around the body, giving them a constant pro-life signal. In the same way as humans need to be able to breathe to use oxygen, T cells need to see ‘self’ to be sensitive to growth factors.

In addition to IL-7, which they need to survive, T cells also need IL-2, a growth factor that allows them to proliferate when they respond to a pathogen.

“The killer T cells we discuss are known as CD8 cells. When they start to mount an immune response, they must interact closely with another population of T cells known as CD4 cells, which give them IL-2,” explained Sprent.

“So you can see how sensitivity to growth factors is very important for CD8 cells, not only to survive, but to function. They really can’t do anything unless they get IL-2. And this is where the importance of lipid rafts comes in.”

“We found it very interesting that within 15 minutes of CD8 cells being exposed to IL-2 in culture, IL-2 receptors on the cell membrane moved to lipid rafts and tethered themselves inside. Rafts are hot spots of signalling activity in cells, with all sorts of specialised fat molecules and proteins clustered together that make signalling efficient. Once IL-2 receptors are housed inside lipid rafts, their signals increase markedly and the immune system gears up to go. ”

“That’s basically the story.”

Curiouser and curiouser. And there’s not even a rabbit hole. Perhaps lipid rafts will provide us with the golden key to the tiny door that will show us much, much more.



PHOTOGRAPH

Thanks to Associate Professor Katharina Gaus from the University of New South Wales for providing the photograph of lipid rafts on this page



ABOUT GARVAN
The Garvan Institute of Medical Research was founded in 1963. Initially a research department of St Vincent’s Hospital in Sydney, it is now one of Australia’s largest medical research institutions with nearly 500 scientists, students and support staff. Garvan’s main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology, and Neuroscience. The Garvan’s mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan’s discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.