As an immunologist, what do you focus on in the immune system?
KUPFER: We study the brains of the immune system, the T cells. These are white blood cells that continually monitor the body for pathogens and instruct the rest of the immune system how to behave during an attack. We are looking for certain molecules in the T cells that act as master regulators to control how the T cells respond to invaders and can be used as therapeutic targets to treat autoimmunity or to use for immune suppression after a transplant to prevent an immune response against the implanted tissue or stem cells.
The immunosuppressants currently available are nasty drugs that suppress the entire immune system. The patients on these drugs become immune compromised and susceptible to normally minor infections.
Our idea is to target specific molecules in the T cell’s machinery that would allow us to only eliminate certain T cells without affecting the rest of the immune system. I am also affiliated with the Institute for Cell Engineering and this goal is directly in line with their mission.
KUPFER: We are preparing for one day when stem cells will be used as clinical therapies. Therapeutic stem cells may come from other sources and not from our own bodies. Injection of these stem cells may cause the immune system to mount a response, and we want to find a way to stop these cells from being rejected in a way that is safe for the patient.
Have you identified any potential therapeutic targets?
KUPFER: Yes. We are interested in protein kinase C theta. We removed PKC theta in mice and the mice developed normally, but their T cells were completely unresponsive to signals alerting them that a pathogen was present. Several pharmaceutical companies are looking into developing molecules that inhibit PKC theta as new types of immunosuppressants. We are looking for proteins that interact with PKC theta to see if they may also be viable therapeutic targets.
The immunological synapses are
the bright green spaces between
the larger antigen presenting
cells and the smaller T cells.
You are credited with first discovering the immunological synapse. What exactly is this structure?
KUPFER: The immunological synapse is the structure at the interface between the T cell and the antigen presenting cell, or APC for short, which activates the T cell in preparation for an attack from a pathogen. The APC presents the T cell with a molecule or short protein that the T cell uses to identify a pathogen -- think of it as showing the T cell a “wanted” poster. At the inner surfaces of the T cell and the APC, the proteins from one cell meets up with proteins of the other cell and form a curious pattern of concentric circles that resemble a bull’s eye to pass on the message for the T cell to activate. If this pattern of proteins is disrupted in any way, the T cell commits suicide, preventing it from further propagating the immune response. If the message is successfully relayed, then the T cell will seek out a pathogen, make antibodies and instruct the rest of the immune system. The T cell master regulators that we are searching for are found in the immunological synapse.
--Interviewed by Vanessa McMains
Abraham Kupfer on curbing overactive immune systems: