SUPPRESSOR T CELLS IN HAPTEN SPECIFIC IMMUNITY

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The objective of this grant is to analyze the relationship between H-2 encoded gene products and VH like gene products which are important in suppressor T cell (Ts) pathways. The relationship between I-J determinants and idiotypic elements on first order Ts cells will be examined in a series of F1 hybrids to examine the preferential assortment I-J and VH structures which are present on suppressor molecules (TsF). The genetic basis of H-2 restriction which occurs between second order (Ts2) and third order (Ts3) cells will be examined by evaluating the genetically restricted inductive signals for Ts3 generation. Moreover, by generating Ts2 and TsF2 in a panel of inbred strains and examining the ability of such generated TsF2 to function in F1 hybrids or other inbred strains, we will determine the H-2 loci which govern Ts2 activation and function. Moreover, the special role of I-J+ antigen presenting cells (APC) will be deduced using an in vitro cytotoxicity assay in which we can selectively manipulate APC activity. We will also characterize the functional and structural properties of two long-term Ts hybridomas. We will evaluate in ivitro and in vivo function at each level of pruification and characterization. Finally using a molecular biological approach, we will evaluate the activity and structure of proteins translated by purified and isolated mRNA obtained from these hybridomas. The major thrust of these studies is therefore to analyze the immunobiology of Ts cells and their products in hapten specific immunity.