Listeria Epitopes TCR Transgenics Antigen Sensitivity and Early Signaling

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In the past 30 years or so, intensive work on T cell responses to 'model' antigens has resulted in a great deal of insight into T cell biology and function, particularly as it relates to the recognition of specific peptide-MHC complexes through the T cell receptor for antigen. Of particular relevance to this project, there is now good evidence that mature T cell blasts are sensitive to even a single molecule of an agonist (peptide-MHC) ligand and that this extraordinary sensitivity is at least in Dart achieved by the engagement of particular endogenous peptide-MHC complexes together with the agonist in triggering TCR dimerization. We now wish to extend these studies to the analysis of CD4 and CDS T cell responsiveness as different times and with different developmental stages of T cells during Listeria monocytogenes infection in mice. We particularly wish to test the hypothesis that T cells which emerge as dominant during Listeria infection do so because they have superior signaling properties. These studies will involve making a series of CD4transgenics specific for a Listeria LLO epitope and assaying these transgenic cells for sensitivity and ability to be protective throughout. This project will involve the close interfacing between highly quantitative experimental data and state of the art modeling techniques.