Craig M. Sorensen

[22] Antigen-specific suppressor factors from hybridoma cell lines

Publisher Summary This chapter discusses the antigen-specific suppressor factors from hybridoma cell lines. Given the extreme heterogeneity of T cell subsets and the number of antigenic specificities that each subset can recognize, T cell receptors and antigen-specific regulatory molecules are difficult to isolate and characterize. One method for obtaining sufficient numbers of homogeneous populations that are representative of rare cells is the stomatic cell hybridization technique. The two most important requirements for the production of T cell hybridomas are a reproducible, rapid assay system and a well-characterized T cell activity. T cell hybridomas can be constructed which constitutively produce GAT-TsF or GT-TsF that are functionally and serologically identical to factors extracted from or secreted by normal T cells. In addition, monoclonal GAT-TsF and GT-TsF induce specific unresponsiveness by the activation of Ts2 cells. T cell hybridomas are also produced by fusion of Ts2 cells and BW5147.

Antigen-specific suppressor T-cell factors.

Considerable progress has been made in achieving immunosuppression pharmacologically, but because specificity is lacking, the patient is often rendered highly susceptible to infection. On the basis of major advances toward characterizing the biochemical constituents of endogenous suppressor pathways, efforts are being made to provide specificity by designing immunosuppressives.

Cellular Requirements and Mechanisms of Action of Antigen-specific Suppressor T Cell Factors

The cellular requirements and mechanisms of action of antigen-specific suppressor T cell factors have been analyzed using partially purified T cell subsets or cloned T cells lines, B cells and monoclonal sources of antigen-specific suppressor T cell factors. Single chain suppressor factors (TsF1) specific for L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) are unable to suppress antibody responses of helper T cells and B cells directly, but require an Lyt 2+ cell to suppress antibody responses to GAT. These GAT-TsF1 are unrestricted by MHC or IgCH locus genes. Their activity contrasts to two-chain suppressor factors (GAT-TsF2) which are suppressive in the absence of added Lyt 2+ cells, but are restricted by MHC locus genes. The target of the TsF2 is the helper T cell; the activity of cloned helper T cells is inhibited when the cells are pulsed with GAT-TsF2 in the presence of GAT. Moreover, these cloned cells adsorb syngeneic, but not allogeneic, GAT-TsF2 in the presence of GAT. Thus helper cells can serve as targets for MHC-restricted TsF2 and cloned helper T cells can be used as a homogeneous target population to analyze the molecular mechanism(s) of T cell-mediated suppression.