The goal of this research is to understand how the structure of the T-cell receptor determines its range of signaling capabilities. The investigator has chosen a genetic approach to determine which structures of the T-cell receptor (TCR) beta chain are important for signaling in T-cell development and in antigen recognition. The investigator will mutate specific domains and residues of the TCR beta chain and determine the effects of these mutations on T-cell development in thymic organ culture using retroviral vectors, and in transgenic/chimeric mice. Effects of TCR beta chain mutations on T-cell signaling will be measured in T-cell hybridomas and clones recognizing altered peptide ligands. Mutations will be introduced into the transmembrane domain, the variable and constant domain interface, and the constant domain loop.
