STRUCTURE REFINEMENT OF MUTANT VERSIONS OF E COLI ASPARTATE TRANSCARBAMOYLASE

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The projects pursued in this laboratory center on the topics of structure/function correlation of T cell receptors, and signal transduction pathways in effector T cells. Several V* genes have been identified which are used to carry out recognition of defined allospecificities. Tumor specific T cell lines which express a particular T cell receptor have been use to identify tumor specific antigens. This has already led to identification of a mucin molecule (human mucin muc-1) expressed by ductal epithelial cells, and by tumors in an altered glycosylation form capable of stimulating T cell immunity. The structure of mucin is being characterized by NMR and circular dichroism in order to select the optimal vaccine or immunotherapeutic antigen for breast and pancreatic cancer. The effector T cells which we study in both systems respond to antigen stimulation by activating several intracellular signaling pathways. We are especially interested in the PKC pathway as a mean of pr omoting and controlling T cell activation.