Characterization of a human antigen specific helper factor secreted by a T cell hybrid

Antigen specific helper factors remain incompletely characterized and somewhat controversial in part because of difficulties in generating large amounts of homogeneous helper factor. To circumvent this problem, we generated a human T cell hybrid secreting an antigen specific helper factor by fusing tetanus toxoid reactive IL-2 dependent T cells to a 6-thioguanine resistant T cell line, and screening hybrids for secreted tetanus toxoid binding molecules. A hybrid was identified that secreted a methionine containing molecule which bound tetanus toxoid, and which could induce autologous peripheral blood mononuclear cells (PBMC) to produce anti-tetanus antibodies. The helper factor stimulated anti-tetanus specifically and did not induce polyclonal immunoglobulin (Ig) synthesis. Characterization of the putative helper factor demonstrated that it carried determinants cross-reactive with HLA-DR but not Ig, bound tetanus toxoid, and had a molecular weight of 100,000-150,000. These data represent the first report of a human antigen specific helper factor generated with T cell hybrids, and demonstrate the feasibility of this approach. This approach to the generation of specific helper factors produces large amounts of helper factor, and will help in the further characterization of these molecules in human immune responses.