T cells bearing gamma/delta receptors are a minor T cell subset with unknown in vivo functions. We have recently described gamma/delta cells that respond to a syngeneic B cell lymphoma and can induce its differentiation. We now propose to analyze the receptors utilized by these T cells, define their specificity, and determine whether they are restricted. In order to do this we will generate a library of T cell hybridomas and characterize their receptors by biochemical and molecular means. We will attempt to define any specificity they might have for immunoglobulin, heat shock proteins, alloantigens or as yet undefined ligands. We will also establish whether they are restricted to MHC molecules or to related Class I molecules such as CD1. Since we have found that these gamma/delta cells can provide help for B cells, we will determine if they can be triggered by nontransformed cells of various phenotypes. We are particularly interested in determining if these gamma/delta cells normally interact with, and regulate, B cells. If a transgenic mouse with functional T cells using these gamma/delta receptors can be constructed, we will determine if it has an altered pattern of immune reactivity, e.g., an altered repertoire of antibodies or TCR usage. We feel that recent data showing that in individuals (and mice) with chronic inflammatory disease, including some forms of autoimmunity, there can be profound alterations in the gamma/delta T cell population, indicates the relevance of these studies to our understanding of the pathogenesis of these diseases.
