News and Research
Immune System
Researchers Identify Protein That Regulates Killer Cells
6-21-2002
Researchers at the University of Toronto and Mount Sinai
Hospital have identified a protein that plays a critical
role in the regulation of "natural killers cells"
in the immune system's battle against foreign and diseased
cells.
"Our
research is a small part of the larger problem of how viruses
and diseased cells ravage the body and circumvent our immune
system," says Kathleen Binns, a U of T doctoral student
in medical genetics and microbiology and an author on a
paper in the June 20 issue of Science.
Using
mass spectrometry, Binns, who does research in the Samuel
Lunenfeld Research Institute at Mount Sinai and MDS Sciex,
sequenced and identified a mystery protein from co-researchers
at the Swiss Federal Institute of Technology in Switzerland.
Once
identified, the protein (SSPase) was sent back to the Swiss
researchers where they cloned its gene and sequenced its
DNA. That gene, they discovered, is a key component involved
in regulation of "natural killer cells" - cells
produced by the body's immune system that attack foreign
or mutated cells like caused by viruses or cancer.
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"This research gives us a better understanding
of how the immune system works. As a result, we have a better understanding
of how viruses and cancer try to get around this process. One day,
we will hopefully be able to develop treatments and therapies to counter
these rogue cells," says Binns.
A group of genes called the major histocompatibility
complex I (MHC-I) are a natural part of the immune system and present
in most cells in the body, explains Binns. Acting like an information
relay, the MHC-I molecules retrieve bits and pieces of the proteins
from inside the cell and display them on the cell surface. "MHC
complexes essentially give a read out of what's inside the cell,"
she says.
T-cells, one of the main components of the immune
system, "examine" the protein fragments on the cell surface
and if they recognize them, the T-cells move on. If, however, the
T-cells do not recognize the fragments, the cell may be hosting a
virus or manufacturing mutant proteins (as in the case of cancer).
The T-cells then react by attacking and killing the "diseased"
cells.
Some virus and tumor cells, however, have evolved
mechanisms that circumvent the T-cell attack by stopping MHC production
and the display of disease proteins, says Binns.
As a countermeasure, the researchers found that the
immune system developed a monitor that employs the SSPase protein
and uses a second type of immune cell known as a natural killer cell,
she notes. The protein processes MHC-I molecules to make a peptide
signal. If sufficient levels of the MHC-I protein are present in the
cell, the natural killer cell moves on. If, however, the killer cell
detects insufficient levels of the MHC-I protein because it has not
received the particular peptide signal, the killer cell attacks and
destroys the suspect cell.
"This process is a check on viruses and abnormal
cells that try to bypass the T-cell system," says Binns. "Viruses
become smarter, our immune systems work to counteract them and the
viruses get smarter again. There's this constant evolution for the
drive to survive, and viruses and cancer cells have the same drive
to survive that we do."
Binns conducted the research with Andreas Weihofen,
lead author on the study, Marius Lemberg and Bruno Martoglio of the
Institute of Biochemistry at the Swiss Federal Institute of Technology,
and Keith Ashman, an investigator at the Samuel Lunenfeld Research
Institute at Mount Sinai Hospital.
This research was funded by the Natural Science and
Engineering Research Council of Canada and MDS Sciex, the Swiss Federal
Institute of Technology and the Swiss National Science Foundation.
This
story has been adapted from a news release issued by University Of
Toronto, www.utoronto.ca.
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