Immune Cells Bombard Infections and Cancers With Numerous Proteins Engulfed in Them

One of the important cells of the immune system are the T cells. They are also known as the killer cells, due to their ability to destroy cells that are infected as well as cancerous cells. How exactly the T cells perform their aggressive tasks of destroying the diseased cells, still remains a question to ponder upon. One of the mechanisms, as revealed in a latest study says that the T cells have proteins inside them that are packed with deadly chemicals which unleash an attack on the target cells. The research was published recently in Science.

One of the earlier known mechanisms is that the T cells have adopted over the course of evolution in destroying the target cells is through perforin, a protein that makes punctures in the outer membrane of the target cell. Along with it, an enzyme, named granzyme, released by the T cells enter the punctured target cells and make them commit suicide. What has remained unknown so far, was whether T cells simply release granzyme and perforin or rely on other specialised structures to transport the lethal molecules to the target cells.

To find out these minute details of modus operandi of the T cells, immunologist Michael Dustin of Oxford University and the corresponding author of the research tracked molecules that are spilled by the attacking killer T cells. The results of the research suggest that T cells package the molecules into containers, which the team has named as the ‘supramolecular attack particles’ or the SMAPs. Intriguingly, they found that these containers not only have perforin and granzymes inside them, but also more than 280 other proteins. This in simpler terms can be viewed as a protein bomb attack by the T cells.

The team of researchers resorted to a type of super resolution imaging technique known as the ‘direct stochastic optical reconstruction microscopy’ to have a detailed closer look at the structure of the SMAPs and their functioning. The high-level imaging technique can pin point individual tiny molecules. Cells can release some small particles wrapped in lipids, but the SMAPs have a protein coat and have granzyme and perforin in their core. The T cells, as concluded by the researchers, instead of applying simple leakage of perforin and granzyme, use a complex receptacle to deliver them.

Further in the research, Dustin and his colleagues attempted to simulate the interactions between killer T cells and their targets. For this, they released the T cells on a double lipid layer, which is similar to the membranes that encloses the cells. The SMAP s were found to have rapidly showed up on the membrane, which is indication that T cells begin to discharge the SMAPs quickly after latching on.

When the T cells were taken out off the surface some of the SMAPs still remained behind. They could kill cells for upto one day, the researchers found. The existence of something like the SMAPs were somehow detected way back in 1980s, but, till now, researchers did not have the imaging technique to decipher their exact structures.

The paper deserves the credit of bringing out a new paradigm for how perforin and granzymes converge at the membrane of the target cells.

“SMAPs’ complex contents suggest they may also have other functions. For example, the particles contain molecules that attract immune cells and manipulate their behaviour, hinting that communication could be one of their roles. We know they are important for killing, but we suspect it’s more than that.” said Dustin.

However, the point that remains unexplained in the study is whether the T cells make SMAPs and then release them or they release the components which later assemble on the target cell surface.