This Special Emphasis Research Career Award (SERCA) application is submitted by a veterinarian who has partially completed a PhD program in the Division of Immunology at the Graduate School of Arts and Sciences at Harvard University. The candidate's long term interests lie in the use of animal models to develop and test new immunotherapeutics, particularly with relevance to cancer. The proposed research will use cellular and molecular techniques to elucidate the requirements for the induction and maintenance of memory CD4+ T lymphocytes. Gaining insight into these factors is important to both human and animal health, as defining the necessary elements for memory cell generation will allow for the development of novel immunization strategies for a wide array of infectious diseases, as well as for the engineering of more effective tumor vaccines. The proposed research will utilize mice expressing a transgenic T cell receptor (TCR) specific for a peptide derived from ovalbumin (OVA). Specifically, the aims of this project are to definitively characterize the phenotype, cytokine production, and expression of genes associated with survival and apoptosis in memory cells in vivo; to determine how the nature of the antigen, costimulation mediated by antigen-presenting cells or extracellular matrix molecules, and cytokine environment influence the induction and survival of memory T cells; to test the ability of plasmid DNA constructs encoding OVA, as well as other costimulators identified as positive regulators of T cell memory, to induce functional memory in vivo; and to develop vaccines for protecting against the outgrowth of OVA-expressing tumors. This research project will be conducted under the direction of Dr. Abul Abbas, Professor of Pathology, Harvard Medical School and Brigham and Women's Hospital.