gamma/deltaT cells contribute to host immune competence distinctly, but their function remains undefined. Our last granting period yielded the first description of a gamma/deltaT cell population that could potentially mediate immune regulation through cross-talk between lymphocytes and immune protection through clearing infected cells with an activated phenotype. For these studies, we generated a monoclonal antibody specific for the non-classical MHC class I molecule T10, and a related molecule T22, as well as a tetrameric T10/T22 specific gamma/deltaT cell staining reagent. We showed that the expression of T10/T22 is activation induced and that they are ligands for a sizable population (about 0.1-2%) of gamma/delta T cells in unimmunized mice. Our goal is to use this system to study (i) the molecular basis of gamma/delta TCR-T10/T22 interactions; (ii) how this self-reactive TCR repertoire is regulated by ligand expression; and (iii) how T10/T22 specific gamma/delta T cells fit into the context of an immune response to Influenza virus infection. A clear understanding of how a useful gamma/delta TCR repertoire is regulated and how the T10/T22 specificity fits into the context of an immune response will shed new light on the role of these cells in the immune system. Moreover, as the T10/T22 specificity has many of the features expected of regulatory T cells, elucidation of the molecular mechanisms governing their activities should prove relevant to immunity in the contexts of tumor surveillance, autoaggression, and infection.