T lymphocytes divide and differentiate when they receive an appropriate activation signal. This signal can be provided by a clonally-distributed, specific antigen receptor (Ti-T3), or through certain broadly distributed cell membrane structures. Molecular biological and in vitro cell culture techniques have been used to investigate the expression of the genes encoding these activation structures, and to study the relationship between structure and function. We have shown using DNA-mediated gene transfer that the clone- specific alpha beta heterodimer completely defines the dual antigen and MHC molecule specificity of mature peripheral T cells. Additional transfection studies have revealed what appears to be a relatively independent contribution of the two V regions of this single receptor to the dual specificity, raising the possibility that the germline repertoire of receptor gene segments is preselected for certain contributions to the ultimate receptor specificity, and that the two chains contribute in a different way to the receptor's recognition potential. Studies of T cell receptor gene expression during ontogeny or T cell maturation in the mature thymus suggest that repertoire selection occurs intra-thymically. These studies also have led to the identification of a new subset of T cell with a distinct receptor termed gamma-delta. Analysis of long term lines of these latter cells shows them to have many of the same effector functions as alpha beta-expressing T cells, but their specificity remains unknown. Investigation of the mechanism of activation of T cells by monoclonal antibodies to non-Ti-T3 surface structures such as Thy-1 revealed a strict dependence on the simultaneous surface expression of Ti-T3. T3- cells could not be stimulated by anti- Thy-1 or Ly6 antibodies, and constitution of T3 expression by gene transfer led to reacquisition of the ability to be stimulated by these antibodies. These studies will enhance our knowledge of which cell membrane molecules are involved in triggering T cells to exert regulatory and effector function, and our understanding of the structural basis for specific T cell responses to antigen.
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