Epstein Barr virus is the cause of infectious mononucleosis and is associated with a number of cancers including Hodgkin's disease and Burkitt's lymphoma. Chronic active Epstein-Barr virus is a rare disease in which persons have persistent organ disease due to the virus that lasts for more than six months. We are studying patients with chronic active Epstein-Barr virus to try to determine the cause of this disease. X-linked lymphoproliferative disease is an immune deficiency disease that is characterized by uncontrolled primary Epstein-Barr virus infection. Patients develop fulminant infectious mononucleosis and often die of this disease. The disease is due to a mutation in the cellular SAP gene. In collaboration with investigators at Washington University, we have been studying how the SAP protein interacts with other cellular proteins to mediate immune responses and killing of target cells. In addition, we have used cells from patients with X-linked lymphoproliferative disease to show that a newly identified receptor (termed CRACC) on the surface of T lymphocytes (cytotoxic T cells) can mediate its activity in the absence of the SAP protein.