The specific immune response to bacterial infections have been shown to involve the generation of both cellular and humoral immunity directed against bacterial antigens. The activation of these immunologic effector mechanisms is accomplished by the interaction of inducer T cells with immunologic effector cells, either B cells, T cells, or macrophages. Severe adult Periodontal disease is a disorder characterized by the inability to resolve the infection by a pathogen or pathogens within the gingival margins and the periodontium which results in a chronic destructive immunologic response. Bacteroides Gingivalis, a black pigmented gram negative bacteria, has been implicated as one of the major causative agents in severe adult periodontal disease. This proposal describes studies that investigate the nature and specificity of T lymphocyte response to fimbrillin, the constitutive protein of fimbriae of B. Gingivalis strain 381. T cells recognize antigen on antigen-presenting cells as peptides associated with self-molecules encoded by the Major Histocompatibility Complex. Therefore, the immunogenicity of whole Bg, bacterial fimbrae, or purified fimbrillin molecules will be analyzed, and factors influencing the immunogenicity of these molecules compared. Small -synthetic peptides of the fimbrillin molecule from B. Gingivalis strain 381 will be generated based on the predicted amino acid sequence from the cloned fimbrillin gene, and these peptides will be analyzed in order to identify specific amino acid sequences, i.e. epitopes, on the fimbrillin molecule which induce immunologic responses in T lymphocytes. The nature of the T cell response to immunologic epitopes will be analyzed for its specificity for MHC-linked molecules, its production of inflammatory and humoral lymphokines, and its ability to respond to Bg, fimbrae, or fimbrillin antigen on a variety of different antigen presenting cells. Understanding the factors which influence the immune response to immunogenic epitopes on fimbrillin will significantly enhance our understanding of how T cells respond to bacterial antigens in .vivo, and will aid in designing better immunologic -approaches to the treatment of periodontal disease.
