Rewrite the textbook! Science: T-cell protein "bomb" detonates infection and cancer - a new mechanism for T-cells to kill bacteria and cancer cells

June 1, 2020 /
BiovalleyBIOON / -- The killer T-cells of our immune system are named hereThey destroy infected cells and cancer cells, and now research has revealed the mechanisms and details of how they kill cancer cells andbacteriaCells bombard targets with protein "bombs" filled with deadly chemicalsDavid Masopust,ofImmunology at the University of Minnesota School of Medicine, said the study is "clearly an important step in improving our knowledge" and reveals how these immune sentinels remove dangerous cellsOne of the most important weapons ofkiller T-cells is perforatin, a protein that pierces the outer membrane of the target cellAn enzyme called granulase released by T cells can also flood in, causing cells to commit suicideIt is not clear whether killer T-cells simply eject granulases and perforated proteins, or rely on special structures to transport deadly molecules to target cellsimage source: STEVE GSCHMEISSNER SOURCESOURCE
To find out, Michael Dustin, a
immunologist at Oxford University, and colleagues tracked the killer T-cell release molecules being attacked Their findings, published recently in the journal Science, show that these cells package molecules into containers, a group called supramolecular attack particles, or SMAPs By analyzing the payloads of these bombs, the scientists found that SMAPs containnot only perforated proteins and granulases, but also more than 280 other proteins to study the structure of SMAPs in greater depth, the researchers turned to a hyper-resolution imaging technique called a direct random optical reconstruction microscope, which can pinpoint individual molecules Cells release small particles wrapped in lipids, but SMAPs have a protein shell and contain granulases and perforatins in their core The researchers concluded that killer T-cells did not simply release perforated proteins and granulases, but formed a complex container to transmit them to simulate the interaction between killer T cells and affected cells, Dustin and his team placed T-cells on a double-layer lipid that resembled a membrane that envelops cells SMAPs appear rapidly on the cell membrane, indicating that T cells begin to release SMAPs after locking the cells some SMAPs still exist when researchers remove killer T cells from the surface Like molecular mines, the team reports, they can kill cells for up to a day Dustin said studies dating back to the 1980s may have found signs of SMAPs, but until recently, researchers had no imaging technique to detect the structure of SMAPs Christopher Mody, a
immunologist at the University of Calgary at the University of , says the paper is commendable for how perforatin and granulated enzymes aggregate on the cell membranes of target cells However, he cautions that the authors have not yet proven whether killer T-cells are manufactured and then released sMAPs, or released and then assembled into SMAPs on target cells Dustin says the complexity of SMAPs suggests they may have other features For example, these particles contain molecules that attract immune cells and manipulate their behavior, suggesting that one of their effects may be communication "We know they're important for cell killing, but we suspect more than that," Dustin said (biovalleybioon.com) Reference: Balint et al.
Supramolecular attack sare ar sylwedd yn dweri cytotoxic T cells.
Science 07 May 2020: eaay9207 DOI: 10.1126/science.aay9207
Immune cells blast infections and with with protein bombs '