Sarcoidosis is a granulomatous disease that affects millions of people worldwide. Although its cause remains unknown, there is ample evidence implicating CD4+ T-cells in its pathogenesis. To gain insight into the antigen (Ag) that activates T-cells in the human lung, the candidate biochemically purified an array of T-cell dependent (Td) antigens from bronchoalveolar lavage (BAL) of sarcoidosis patients and further purified a fraction of these Ags containing universal sarcoidosis T-cell epitopes (termed profile#68, P68). These purified Ags induced blastogenesis, cytokine production, DNA replication, and cell division in T-cell lines derived from BAL of sarcoidosis patients, but not in T-cell lines derived from BAL of control patients. Two logical and mechanistic specific aims are proposed that follow directly from the preliminary data: 1) To produce T-cell lines specific for universal sarcoidosis epitopes contained in P68-Ags and, 2) To identify the molecular species that induce recall in P68 specific T-cell lines. The applicant is a Hispanic, US-citizen, M.D., Ph.D., board certified in Internal Medicine, Pulmonary Diseases, and Critical Care Medicine, recipient of a MIRS award and a fellowship from the American Thoracic Society. The applicant is pursuing training in molecular immunology proteomics and molecular genetics, focusing of pulmonary immunopathogenesis through the specific research project proposed in this grant. The sponsor is Barry Fanburg, M.D., who has been actively engaged in pulmonary research and sarcoidosis for over 25 years. Brigitte T. Huber, Ph.D., Professor of Pathology and renowned world expert in molecular immunology and proteomics, is a mentor. Mathews Waldor M.D., Ph.D., expert in molecular genetics, is a collaborator. The applicant will have structured training activities, including didactic work, seminars and periodic meeting with the advisory committee. The applicant will use facilities and laboratory equipment in the sponsor and collaborators laboratories located at the Tupper Research Institute, and Tufts University School of Medicine attached to the New England Medical Center. Award of this grant and completing the research plan will aid in the identification of the cause of sarcoidosis and prepare the applicant for a career as an independent investigator in pulmonary immunopathogenesis.
