Biography
Mark Davis is Director of the Stanford Institute for Immunology, Transplantation and Infection (ITI), is a professor of microbiology and immunology and a Howard Hughes Medical Institute investigator. He is well known for identification in the 1980s of the elusive T-Cell receptor genes, which allow T lymphocytes to fight disease causing microbes, and he and his group have made many subsequent discoveries about this type of molecule and how it functions. He and his group have also discovered a number of other important genes expressed by lymphocytes, including BLIMP-1, the first master regulatory gene in these cells and, with Dr. Alan Krensky, Granulysin, an important natural defence against tuberculosis. Dr. Davis has also pioneered the development of diagnostic assays for immune function, first with the development of peptide-MHC tetramers which allows the precise quantitation and characterization of T cells from clinical samples and more recently, with Dr. Patrick Brown and Dr. Yueh-hsiu Chien the invention of a high throughput cellular array system, which can obtain information about many different types of blood cells simultaneously.
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Deconstructing T Cell Recognition
My laboratory is interested in understanding how specific helper and cytotoxic T cells recognize target antigens and complementary molecules on other cells. This can also be considered a model system for the molecular basis of transient cell-cell recognition. In particular, we have developed a method to “count” the number of agonist peptide-MHC ligands that a given T cell “sees” and what the consequences of this are on a cell-by-cell basis. We find that all of the T cells surveyed are able to detect even one peptide-MHC ligand and that this sensitivity is dependent on synergy with certain endogenous peptide-MHC complexes—at least in CD4 + T cells. We also find that an irreversible commitment to a particular course of action, such as cytokine secretion or killing, requires a certain number of ligands which defines a ligand threshold shared by other cells of that type. These thresholds also change with T cell development, and we find that we can manipulate them in a number of ways, including altering the steady state levels of a particular micro RNA. We conclude that lymphocytes in the aggregate act as a sensory “organ” precisely geared to distinguish foreign entities against a diverse background of endogenous molecules.
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