T cells are absolutely essential to the development and regulation of immune responses and consequently to the maintenance of health. Our knowledge of the diversity and biological activity of T cell subsets is extensive; yet, very little is known about the structure of T cell receptors and T cell mediators. The objectives of this proposal are to isolate, purify, and characterize antigen-specific factors and receptors expressed by various subsets of suppressor T cells. Our strategy for the analysis of murine suppressor T cell products was to develop T cell hybridomas by screening for suppressor activities analogous to suppressor activities of normal T cells. We have produced a large panel of T cell hybridomas that very likely contains a minimum of four distinctive T cell subsets. Factors produced by these hybridomas have antigen-binding sites and bear determinants encoded by the H-2 gene complex. Six different H-2 haplotypes are represented in this panel. We propose to characterize T cell products from these hybridomas using functional serological, immunochemical and biochemical techniques.
Our specific aims are to determine the structure and amino acid sequence of a prototype suppressor factor which we have purified to homogeneity. Comparisons among selected T cell hybridoma products will reveal the degree of structural homology between members of a family of closely related molecules. We will develop new serological reagents by immunization with T cell hybridomas or purified hybridoma products. These sera and mono-lonal antibodies will be used to identify new I-region gene products and to verify that factors and receptors produced by T cell hybridomas are expressed by analogous, normal regulatory T cells in vivo. These studies should eventually lead to the identification of all essential, interacting T cell subsets in one antigen-specific suppressor pathway. In addition, questions concerning the number and nature of the genes involved in suppressor T cell activity can be approached using these suppressor T cell hybridomas.
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