The long-term objective of this research is to elucidate the biological functions of the self-reactive T cells that recognize the idiotopes (Id) of immunoglobulin molecules. These Id- specific T cells (TId) are perceived as the major regulators of antibody response to bacterial antigens and, perhaps, as immunosurveillance cells for the Id-positive lymphomas. The proposed project was fueled by a new method for establishment of stable T cell lines/clones that specifically recognize the idiotopes of the T15 immunoglobulin. The T15-specific TId lines have been derived using syngeneic B cell lymphoma transfected with the T15 genes. Since the T15 molecule is the prototype of the antibody that protects mice against S. pneumonial (Pn) infection, the availability of T15-specific TId opens the way to fully elucidate the regulation of T15Id + B cell response to Pn. Moreover, the receptor specificity and properties of autologous TId can now be formally studied.
The first aim i s to determine the TcR structure and the fine specificity of TId lines/clones and to elucidate the response of these T cells to various forms of Id molecules, both soluble and cell-bound. Secondly, the regulation of antibody response to Pn by the TId lines/clones will be studied in vitro, in order to determine the mechanisms by which the TId stimulate and/or suppress the functions of the Id+, Pn-responsive B lymphocytes. The collaboration of TId, with antigen-specific T helper clones in regulation of antibody response will also be studied, using lymphocyte cultures immunized with various forms of the Pn antigen.
The third aim i s to determine the biological significance of TId in vivo using (a) adoptive transfer of TId lines/clones into nude mice, (b) measurements of the frequency and localization of TId in normal and T15-transgenic mice, and (c) deletion of various TId subsets, in situ, followed by Pn immunization. The last aim is to explore the cytostatic (growth-inhibitory) effects of TId lines/clones on Id+ B cell lymphomas in vitro and the protection of mice against the transplanted tumors.
