Immunologists Professor Dr. Mark M. Davis, Stanford University,
Califomia, U.S.A., and Professor Dr. Tak W. Mak, University of Toronto, Canada, will
received the Paul Ehrlich and Ludwig Darmstaedter Prize for 2004, endowed with a total of
€ 100,000, for their discoveries on the specificity and fimction of the T cell receptor. This was
resolved by the Scientific Council of the Paul Ehrlich Foundation. The prize, was presented
on March 14, 2004 in the Frankfurter Paulskirche, is one of the most important and
internationally renowned awards conferred in the Federal Republic of Germany in the field of
medicine.
An efficient immune system is essential to survival. If it fails, the result is almost inevitably
death, usually due to serious and recurrent infections. The cells and molecules of this
resistance system patrol constantly throughout the human body in search of health-damaging
pathögens and other alien substances. They can recognize, track down and incapacitate a
practically unlimited number of alien cells and substances. Moreover, they can "remember"
each infection, so if it recurs they can respond faster and more effectively.
The specific, so-called "adaptive" part of our immune system consists of two arms: the
antibody-producing B lymphocytes and the T lymphocytes. The B cells are the effector
molecules of the so-called "humoral" immune response; for a specific immune reaction, they
need the help of T cells. The T cells are responsible for the cell-mediated immune response;
through T cell receptors they correspond with the antibody-producing immune cells, the
macrophages, and the so-called "dendritic" cells, and thereby stimulate them.
Numerous researchers have spent many years trying to identify the molecules and genes
responsible for the T cells' targeted defence response. It was considered certain that the
activity of T cells is triggered through the T cell receptor on their plasma membrane as soon
as it binds a specific antigen that matches it just like a key fits a lock.
Both prizewimers have done ground-breaking work in this area: Mark M. Davis "searched"
for T cell receptor genes in T lymphocytes of mice, while Tak W. Mak used human T cell
lines for his experiments. The starting point for their work was the idea that T cell receptors
are only formed in T cells, but not in B cells. In a series of elegant experiments, Davis and
Mak showed that T lymphocytes have their own genetic capacity to produce millions of
different antigen-specific T cell receptors. The two scientists and their teams identified and
sequenced certain T cell receptor genes. From their analysis of these genes, they were able to
derive many structual details of the T cell receptor.
In other experiments, Mark M. Davis developed cellular and molecular techniques that made
it possible to examine the antigen-specificity of T cells in tissue when T cells bind their
specific antigens. Parallel to this, Tak W. Mak examined the importance of selective gene
deletions -where parts of a gene and thus the genetic infomation it contains are removed -
for the function of the immune system, and especially for T cells, with the help of so-called
"knockout mice", in which the functions of certain genes have been deactivated.