application): The candidate is currently enrolled in his second year of a clinical and research fellowship at the Massachusetts General Hospital. He holds degrees in bioengineering and molecular biology from the University of California, Berkeley, an M.D. from Columbia University, and completed his residency in medicine at Duke University. The candidate aspires to a career as a basic science researcher at a major medical center, with a dominant research focus complimented by clinical responsibilities. The bulk of time would be spent in research. The environment in which the proposed research training program will be accomplished will provide a supportive atmosphere with ample opportunity for formal learning and collaboration, and will prepare the candidate for an independent investigative career. The research is aimed at characterizing the nature and function of HIV-1 specific T-helper cell clones derived from individuals with acute and long-term nonprogressive infection, and chronic infection after therapeutic vaccination. The focus of the work will center on identifying the breadth, specificity and unique attributes of the T-helper cell response to acute and long-term nonprogressive HIV-1 infection, using both cellular and molecular techniques. Access to the unique cohorts of HIV- 1-infected persons undergoing structured treatment interruptions will provide novel insights into the role of T helper cells in control of viremia. HIV-1-specific CD4+ lymphocytes will be isolated and cloned from individuals identified with acute HIV-1 seroconversion illness, those with long-term nonprogressive infection, and those treated with therapeutic vaccination. The clones will be analyzed in detail, monitoring their cytokine and chemokine production, fine epitope specificity, HLA restriction, and cytotoxic potential. The fate of specific T cell clones will be followed in acute infection using oligonucleotide probes to track individual T cell clones and correlated with the development of an effective immune response, both during treatment and following treatment interruption. The knowledge to be gained regarding the generation and function of CD4+ T lymphocytes may further the understanding of HIV immunopathogenesis and shed insight into potential vaccine development and immunotherapeutic approaches.
