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18 HEALTH AND LABORATORY MAGAZINE
A NEW TECHNIQUE
REVEALS HOW
IMMUNE CELLS
LOCATE THEIR
TARGETS
MIT biological engineers have
developed a simple way to identify
B or T cells that interact with viral or
bacterial proteins.
The human body has Michael Birnbaum, an “In your body, you have researchers modified the with antigens from 100
millions of unique B and T associate professor of millions of unique T cells, VSV-G protein so that it different viruses, including
cells that roam the body, biological engineering and they could recognize cannot infect a cell on its influenza, cytomegalovirus,
looking for microbial at MIT, a member of billions of possible own, instead relying on an and Epstein-Barr virus.
invaders. These immune MIT’s Koch Institute antigens. All of the tools antigen of the researchers’ They screened these
cells’ ability to recognize for Integrative Cancer that have been developed choosing. This modified viruses against about
harmful microbes is critical Research, and the senior to this point are really version of VSV-G can 400,000 T cells and showed
to successfully fighting off author of the study. designed to look at one only help the lentivirus that the technique could
infection. side of that diversity at a get into a cell if the paired correctly pick out antigen-
A SIMPLE SCREEN FOR A time,” Birnbaum says. antigen binds to a human T-cell receptor pairings
MIT biological engineers COMPLEX SYSTEM B or T-cell receptor that that had been previously
have now devised an The MIT team set out to recognizes the antigen. identified.
experimental tool that Both B and T cells play design a new tool that
allows them to precisely critical roles in launching an would let them screen huge Once the virus enters, The researchers also
pick out interactions immune response. When a libraries of both antigens it integrates itself into screened two different
between a particular T cell encounters its target, and immune cells at the the host cell’s genome. B-cell receptors against
immune cell and its it starts proliferating same time, allowing them Therefore, by sequencing 43 antigens, including
target antigen. The new to produce an army of to pick out any specific the genome of all the antigens from HIV and the
technique, which uses identical cells that can interactions within the vast cells in the sample, the spike protein of SARS-
engineered viruses to attack infected cells. And realm of possibilities. researchers can discover CoV-2.
present many different B cells that encounter their both the antigen expressed
antigens to huge To create a simple by the virus that infected In future studies, Birnbaum
populations of immune target begin producing way to screen so many the cell and the sequence hopes to screen thousands
cells, could allow large- antibodies that help recruit possible interactions, the of the T or B-cell receptor of antigens against B and
scale screens of such other components of the researchers engineered that allowed it to enter. T cell populations. “Our
interactions. immune system to clear a specialized form of a ideal would be to screen
the infection. lentivirus, a type of virus “In this way, we can use entire viruses or families of
“This technique leads that scientists often use viral infection itself as a viruses, to be able to get
the way to understand Scientists who study the to deliver genes because way to match up and then a readout of your entire
immunity much closer to immune system have it can integrate pieces of identify antigen-immune immune system in one
how the immune system several tools to help them DNA into host cells. These cell parings,” Birnbaum experiment,” he says.
itself actually works, identify specific antigen- viruses have an envelope says.
will help researchers immune cell interactions. protein called VSV-G that In one study that is now
make sense of complex However, these tools can bind to receptors on INTERACTIONS ongoing, Birnbaum’s lab is
immune recognition in a generally only allow for the the surface of many types IDENTIFIED working with researchers
variety of diseases, and study of a large pool of of human cells, including at the Ragon Institute of
could accelerate the antigens exposed to one B immune cells, and infect To demonstrate the MGH, MIT, and Harvard
development of more or T cell, or a large pool of them. accuracy of their to study how different
effective vaccines and immune cells encountering technique, the researchers people’s immune systems
immunotherapies,” says a small number of antigens. For this study, the created a pool of viruses respond to viruses such