Ligand-dependent regulation of T cell development and activation.

Mature CD4+ and CD8 + T lymphocytes develop in the thymus from precursors with diverse clonally distributed receptors, possessing binding sites with negligible, intermediate, or high affinity for selfpeptide major histocompatibility complex (MHC) ligands. Positive- and negative-selection processes acting on this precursor pool yield a peripheral T cell population comprised of cells with receptors (TCR) capable of self-peptide MHC ligand recognition, but largely depleted of those able to mediate overt self-responsiveness. The Lymphocyte Biology Section of the Laboratory of Immunology studies how self-ligand recognition guides T cell development in the thymus and influences the functionality of naive and activated T cells in the periphery. It also seeks to define the molecular basis for the discrimination between self-ligands and foreign antigens that controls T cell activation to effector function. Finally, it uses a combination of conventional cellular immunological methods, biochemical and biophysical studies, and advanced imaging techniques to visualize, quantitate, and model the various steps in the development of primary and memory T cell immune responses.