CYTOTOXIC T LYMPHOCYTE RESPONSE TO HPV 16

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DESCRIPTION: (Applicant's Description) As a student in an M.D.-Ph.D. program at Albert Einstein College of Medicine, Dr. Nakagawa studied the structure function relationships of murine Major Histocompatibility Complex in terms of its immunological and physiological properties. After completing a residency program in laboratory medicine at the University of California at San Francisco, where she still is, she began a research project studying cell-mediated immunity to Human Papilloma Virus type 16 (HPV 16) which is a causative agent of cervical dysplasia and cancer. Data collected thus far, using a T cell proliferative assay as well as a cytotoxic lymphocyte assay, support her working hypothesis that cell-mediated immunity to HPV is instrumental in its elimination and thus is protected against the development of associated diseases. The experiments proposed in this application are nested with an ongoing longitudinal study in which HPV 16 infected women who have not developed high grade intraepithelial lesions are tested for cytotoxic T lymphocyte responses to HPV 16 oncogenic proteins, E6 and E7. The specific aims of this project are to characterize the lymphocyte subset(s) responsible for anti-HPV activity, to eliminate background activity, to explore alternative methods of in vitro stimulation, and to develop a protocol to perform cytotoxic T lymphocyte assay using T cell lines instead of bulk cultures. The last aim will give us a tool to identify immunodominant epitopes of HPV 16 in the future. The long-term goal of this project is to develop effective vaccines and immunotherapy for prevention and treatment of cervical cancer. Dr. Nakagawa's long-term career goal is to continue research in HPV immunology as an independent investigator. She envisions this will be best accomplished by becoming a faculty member at an academic medical center where she will also have clinical responsibilities as a laboratory medicine physician. The University of California at San Francisco, which is a major academic medical institution with many distinguished scientists, offers an excellent environment to develop skills and further her expertise in the field to accomplish her goals.