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