A rigorous program of classroom and laboratory training in molecular biology and immunology is proposed as the basis for a career as an independent investigator in infectious disease. The program will consist of two phases to allow in-depth study of molecular biology and immunology at the graduate level and provide intensive training in the laboratory in order to foster my intellectual development as a physician-scientist. During Phase I graduate courses in genetics, molecular biology, virology, and immunology at Harvard University and the Massachusetts Institute of Technology will provide a didactic framework for the proposed experiments. At the same time, work will commence in the laboratory of Dr. Richard Young of the Whitehead Institute and MIT, who will serve as Phase I sponsor. Dr. Young has been chosen for his expertise in molecular biology and immunology as evidenced by his contributions to the understanding of cellular immunity directed against mycobacterial antigens. Moreover, as a member of the National Cooperative Vaccine Development Group for the Acquired Immune Deficiency Syndrome (NCVDG-AIDS), Dr. Young is committed to applying the resources at his disposition towards the understanding of the genetics and immunology of human immunodeficiency virus (HIV). I proposed to study the epitopes of HIV antigens that elicit a cytotoxic T-lymphocyte (CTL) response from the host. These epitopes will be determined by using vaccinia/HIV recombinants carrying segments of HIV genes and by using a series of overlapping synthetic peptides derived from the predicted amino acid sequences of HIV proteins. In addition, techniques for clonal expansion of HIV-specific cytotoxic T-lymphocytes will be developed. Progress during Phase I will be monitored by a committee of scientists and physicians selected by Dr. Young and Dr. John T. Potts, Chief of Medicine at Massachusetts General Hospital. Dr. Martin S. Hirsch, Professor of Medicine at HMS and leader of the AIDS research group within the MGH Infectious Disease Unit will serve as the Phase II clinical sponsor along with Dr. Robert T. Schooley, Associate Professor of Medicine (HMS) and member of the NCVDG-AIDS. Although specific goals of Phase II are not yet defined, it is expected that the results of the Phase I series will be extended to provide a greater understanding of the cellular immune response to HIV infection.
