NK Cell Function

Why is it so important?

Natural Killer (NK) Cells are a type of lethal lymphocyte. Like cytotoxic T cells, they contain granules filled with potent chemicals. They are called "natural" killers because they, unlike cytotoxic T cells, do not need to recognize a specific antigen before swinging into action. They target tumor cells and protect against a wide variety of infectious microbes. In several immunodeficiency diseases, including AIDS, natural killer cell function is abnormal. Natural Killer Cells may also contribute to immunoregulation by secreting high levels of infuential lymphokines

Both cytotoxic T Cells and Natural Killer Cells kill on contact. The killer binds to its target, aims its weapons and then delivers a lethal burst of chemicals that produces holes in the target cell's membrance. Fluids seep in and leak out, and the cell bursts.

December 8, 1999

BODY'S NATURAL KILLER DEFENSE REVEALED:
ROCKVILLE, MD.

A molecular lock and key complex of so-called natural killer cells in the blood stream has been found for the first time, scientists at the University of Maryland Biotechnology Institute (UMBI) report in today's issue of the journal Nature. Natural Killer (NK) cells are a critical, first line of defense against cancer tumor cells and cells infected with the AIDS virus and other harmful microbes. They have molecules on their cell surfaces called NK receptors that find and destroy diseased cells.

The scients have captured the first real look a the subtle workings of NK cells, says co-author Roy A. Mariuzza, professor and molecular biologist at UMBI's Center for Advanced Research in Biotechnology (CARB) in Rockville, Md. "This tells us for the first time how NK cells recognize the difference between normal and abnormal, infected cells." He says the molecular machinery of NK cells is not as well understood as that of T or B while blood cells for fighting infections, but is also essential for maintaining health. "Lucky for us, there are NK cells", says Mariuzza. Some viruses such as HIV, the cause of AIDS, have evolved camouflaging tricks and can't be destroyed by T cells." The NK cells find and destroy unprotected cells that are infected, those that no longer have markers called MHC molecules on their surface to say they are healthy," he says. The NK cells patrol the bloodstream in all directions like molecular police cruisers, says Mariuzza, using their NK receptors to signal out abnormal cells without proper MHC identification. The NK cell punches the abnormal cell with toxic granules and kills it. At CARB, Mariuzza and collaborators discovered how an NK receptor molecule locks onto MNC molecules, which are on the surgaces of practically all normal cells. Once locked on, the NK cell "knows" the blood cell with the MHC marker is all right. It unlocks, then goes "cruising" off to check out other cells.

The laboratory breakthrough occured when the researchers made a pure crystal of the molecular complex, or the checkup point, of an NK receptor and an MHC marker molecule. They then applied a powerful beam of X-rays to the crystal to compute the positions of the atoms making up the molecular lock-and-key structure. The result was the first 3-dimensional molecular structure known for the interaction of the NK receptor and an MHC marker.

"By identifying the molecular structure, the researchers have validated the missing self hypothesis that NK cells will attach only virus-infected or tumor cells that have lost their healthy self identity" says Jennie Hunter-Cevera, UMBI president.

For medical research, the discovery helps form a more rational way of discovering new disease fighting drugs, says collborator David H. Margulies of the National Insitute of Allergy and Infectious Diseases, part of the National Institutes of Health. Now that the first molecular structure of an NK receptor/MHC linkage is known, says Margulies, DNA researchers can experiment with "changing the molecules to assess how they bind and behave." He comments that the discovery means now "you see exactly what the NK cells sees."

Mariuzza adds, "Our results give us a basis for expanding research on NK cell receptors and MHC. We have actually found two distinct (molecular) binding sites. One was unexpected. Now we need to compare this to still unknown structures of other NK receptors to find out how each of them works."

Scientists estimate that NK cells make up five to 16 percent of the total number of white blood cells that the body uses to fight infections. Those with defective or absent NK cell activity can contract a wide specturm of diseases, particularly cancers. In fact, results from a number of clinical trials indicate that NK cells can be used to control tumor metastates. The therapeutic uses of NK cell activity will likely increase as their relationships to healthy and diseased cells becomes better known.