This grant proposal is intended as a vehicle for preparing a hematologist/oncologist for a career in immunology research. The Physician Scientist Award will provide the financial support required to sustain this training period. The application is structured to provide the didactic and laboratory experiences necessary to succeed as an independent investigator. Coursework equivalent to that required for Ph.D. candidates will be pursued at the Tufts University Sackler School of Graduate Biomedical Sciences. Research will be performed under the supervision of Dr. Judy Lieberman, a hematologist well-versed in T cell immunology, and Dr. Robert Schwartz, an experienced immunologist. The sponsoring Division of Hematology/Oncology currently includes approximately 35 postdoctoral research fellows, and has an outstanding record for training medical investigators. The proposed research project will study the immune control of B cell neoplasia related to the Epstein-Barr virus. We will address the hypothesis that CD8+ T cells (CTL) provide protection against EBV- associated B cell lymphomas via recognition of latent cycle EBV proteins. This work will take advantage of viral-vaccinia technology allowing selection of cytotoxic T cells with precise specificities, as well as a small animal model of human EBV-associated B cell lymphoma. The project is organized in 4 parts: (1) describes the generation and characterization of CTL that recognize specific EBV latent proteins; (2) evaluates the use of EBV-specific CTL in adoptive therapy of EBV-associated tumors in a SCID mouse model; (3) asks whether adoptive therapy by CTL can lead to an escape from immune surveillance by a change in tumor cell expression of EBV-related proteins; (4) describes a population study in which a correlation will be sought between the spectrum of EBV-latent-protein- specific CTL and the development of EBV-positive lymphoma in humans.