Listeria Epitopes TCR Transgenics Antigen Sensitivity and Early Signaling

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