While MHC-restricted T cell interactions with macrophages and B cells have been well-documented, little is known about T-T interactions between T cell subpopulations. During the past grant cycle we isolated and characterized several self-Ia reactive (autoreactive) Lyt 1+2-, L3T4+, Ia- T cell clones from normal unimmunized DBA/2 mice and used them to analyze the hypothesis that a T-T network existed in the normal immune system. These studies led to the unique observation that Lyt 1+2- T cells isolated from normal DBA/2 mice proliferated strongly and directly to syngeneic autoreactive T cells. Most recently preliminary data has indicated that normal Lyt 1+2 T cells respond to allogeneic as well as syngeneic autoreactive T cells suggesting that the T-T network may be """"""""monomorphic"""""""" with respect to class II antigens. Based on these observations studies will be carried out to: 1) Analyze selected characteristics of the T-t interaction between Lyt 1+2-, L3T4+, Ia- T cells and autoreactive T cells. 2) Test the hypothesis that the idiotypic markers of T cell receptors for MHC epitopes are """"""""monomorphic"""""""" within the species. 3) Analyze the rearrangement pattern, expression and sequence of T cell receptor genes for auto- and alloreactive T cell clones/hybridomas with specificity for Iad. 4) Analyze the function of autoreactive T cells and their regulation by Lyt 1+2-, L3T4- anti-autoreactive T cells. These studies will involve preparation of a series of autoreactive and anti- autoreactive T cell hybridomas and analysis of the hybridoma receptors by anti-autoreactive T cells and by anti-receptor monoclonal antibodies. The potential functional significance of Lyt 1+2-anti-autoreactive T cells will be analyzed in vitro to determine the modulatory effects of these cells on autoreactive T cells. Lastly, we will attempt to manipulate mice so as to be able to directly access the biologic effects of autoreactive T cells in vivo. These experiments should provide information relative to network regulation among T cells and its potential role in neoplasia, autoimmunity and regulation of graft versus host disease.
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