Characterize the T cell response to Aa in mice that have been either immunized subcutaneously or orally infected. Aa has been strongly associated with localized juvenile periodontitis and is one of many species of bacteria found in the gingival pocket of patients with adult periodontitis. It has been shown that both cell mediated and humoral immune responses are important in periodontal diseases. There is also a suspicion that an exaggerated immune response could be responsible for much of the destruction seen, i.e., bone loss, soft tissue destruction. What has not been shown is exactly what interaction at the molecular level is seen between T cells and Aa. We propose to utilize hybridoma technology to ask what are the predominant T cell antigenic epitopes on Aa and to determine whether there is a restricted TcR response in mice. Since an oral infection such as periodontal disease allows for the pathogenic bacteria to adhere and colonize the gingival pocket without direct exposure to the host's immune system, we will ask whether the repertoire differs when mice are infected versus immunized. To characterize the immune response to Aa, we will analyze TcR sequences. If several of the hybridomas we raise have T cell receptors with the same V beta but different junctions, the possibility of a superantigenic response exists. Another possibility is that an immunodominant epitope could exhibit conservation in the junction plus the V regions suggesting a predominant antigenic epitope. By correlating the antigenic specificity with the TcR junctional sequences, we can elucidate the regulation of T cell induction in response to Aa infection. These characteristics of the immune response to Aa are all important considerations in vaccine design.
Showing the most recent 10 out of 34 publications
