Our research focuses on the thymic selection, peripheral activation, and tolerance of CD4+ T cells. CD4+ T cells direct cell-mediated immunity by regulating the production of immunoglobulins by B cells and secreting cytokines that regulate the function of inflammatory cells and cytotoxic T cells. The normal development and function of CD4+ T cells is dependent upon engagement of unique antigen-specific T cell receptors by major histocompatibility complex (MHC) class II molecules. The expression of class II molecules is limited to thymic epithelial cells — where they are required for the development of CD4+ T cells — and antigen-presenting cells such as dendritic cells, macrophages, and B cells — where they are required for the survival and activation of those T cells. The laboratory is focused on delineating the relative contribution of the different types of class II-positive antigen-presenting cells to the CD4+ T cell-dependent immune response. To do so, we have developed a series of transgenic mice with restricted expression of the murine MHC class II molecule, I-Ab, and use them to investigate the requirement for different populations of antigen-presenting cells.