Basic questions relating to the role of T and B lymphocytes in adaptive immunity are being explored. There is a strong emphasis upon understanding adaptive immunity at a molecular level in whole animals. Intracellular signaling mechanisms regulating T cell development and activation are being investigated using a variety of genome engineering methods. Immunoglobulin class switch recombination in B cells is being investigated using techniques such as bacterial artificial chromosome transgenesis. The behavior of T cells as regulators of adaptive immune responses and as effector cells is also being examined directly in bacterial infection and organ transplantation models using combined cellular and molecular approaches. We are currently investigating mechanisms involved in processing of antigen for recognition by T cells, including intracellular assembly of major histocompatibility complex class I proteins, and their altered trafficking in virus-infected cells. These studies provide important insights into the function of the adaptive immune system in health and disease.