T Cell Activation, Cell Surface Adhesion Molecules, and Receptor-Mediated Control of Intercellular Recognition
Recognition between different cell types is important in cell-to-cell interactions leading to the initiation of an immune response. These recognition events are often mediated by specific cell surface adhesion receptors which bind to complementary counter-receptors on other cells. Similar adhesive interactions control the migration of T lymphocytes to antigenic sites where they take part in, for example, the rejection of transplanted organs or the clearance of virus-infected cells.
The projects in this laboratory examine the expression and regulation of a number of these membrane receptor proteins that are responsible for intercellular recognition in the immune system. After activation in tissue culture, T lymphocytes down-regulate expression of one specific adhesion molecule while up-regulating a series of different receptors, thus resulting in changes in specificity of intercellular recognition, adhesion, and cell localization. Similar changes take place among T cells rejecting transplants in vivo. Using biochemical methods, cell culture, and flow cytometry (FACS analysis), we are studying the cellular and molecular mechanisms by which T cells regulate these molecules during activation by antigen and the role of such changes in receptor expression in the normal immune response. The models being examined include organ transplant rejection, contact sensitivity, and mycobacterial granulomas. In one model, we are studying transgenic mice expressing a mutant form of one of these molecules to determine its role in migration out of blood vessels in vivo.