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Natural killer cells help understand responses to bone marrow transplants

Published on August 4, 2005 at 7:14 AM · No Comments

Scientists have discovered that a group of important immune system cells has a surprising resemblance to cinematic British superspy James Bond: the cells receive a "license" that allows them to unleash their most potent attacks on enemies.

This licensing process apparently helps reduce the chances that the cells will erroneously direct their firepower at the body's own tissues, according to researchers at Washington University School of Medicine in St. Louis. The process is very different from other previously identified ways that help immune cells distinguish invaders from self, and could have important implications for doctors struggling to understand such issues as persistent viral infections and patients' responses to bone marrow transplants. The findings will appear in the August 4 issue of Nature.

The immune cells in question already evoked cinematic connections simply by virtue of one of their names: scientists commonly refer to them as natural killer cells. The cells rapidly attack invaders and are continually generated in the bone marrow, leading to replacement of the entire population approximately once a week.

Scientists led by Wayne M. Yokoyama, M.D., the Sam J. Levin and Audrey Loew Levin Professor of Research in Arthritis, and professor of medicine and of pathology and immunology, discovered through experiments in mice that the arsenals of natural killer cells only become fully armed after a receptor on their surfaces interacts with a molecule on the surfaces of other cells.

The molecular details of the process were so unusual that Yokoyama and his colleagues found themselves struggling to develop terms to describe it to other immunologists.

"So many other terms that might have been appropriate--education, tolerance, instruction, selection--already have specialized meanings in immunology that really aren't appropriate for this unique process we've discovered," says Yokoyama, who is a Howard Hughes Medical Institute Investigator and chief of the Division of Rheumatology at Barnes-Jewish Hospital. "Many of these terms refer to processes with a similar outcome--improved ability to distinguish between self and non-self--but this is a very different way of reaching that goal. So we came up with the term licensing."

Their results include another ironic connection to the world of cinema spies: the molecular details of the process feature a player who is comparable to a double agent. Scientists have known for some time that natural killer cells have inhibitory receptors on their surfaces.

The natural killer cells' ability to attack is inhibited when these receptors encounter a molecule known as major hiscompatibility complex (MHC) class I on the surface of other cells. MHC serves as a kind of molecular I.D. badge, helping the natural killer cells to distinguish the self from an invader.

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