IMMUNOREGULATION BY ANTI-IDIOTOPES

本研究的长期目标是阐明

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 is 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 is 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.