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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
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