Doherty and Zinkernagel inoculated mice with a virus
causing meningitis. They isolated the immune T killer
cells and found that these had to recognize two
things on the surface of the infected cells in order
to kill them: virus antigen, as expected, but also an
MHC molecule of the infected mouse strain. MHC
molecules are normal components of healthy cells.
They were known to differ among individuals and to
cause rejection of organ transplants and they are
therefore sometimes called transplantation antigens.
It came as a surprise that they were also involved in
recognition of infected cells.
Doherty and Zinkernagel presented two main theoretical models to explain their observations. These models have inspired immunologists and set the stage for research on cell-mediated immunity for at least two decades.
|Wrong combination: the right virus antigen (x) but the wrong MHC molecule (b).|
|Wrong combination again: the right MHC molecule (a) but the wrong virus antigen (y).|
|The correct combination or virus antigen (x) and MHC molecule (a) leads to killer cell attack.|
|A T killer cell (upper right) attaching to and sensing the antigens on a target cell. If the target cell carries the correct antigens fitting the receptor of this particular T cell, the "kiss of death" will follow: the target cell will be destroyed.|