University of California

Cell Genesys, Inc.

Other

Arthur Weiss

Krisztina M Zsebo

Daniel J Capon

Margo R Roberts

Brian A Irving

James Fraser

Chimeric proteins and DNA encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.

Chimeric chains for receptor-associated signal transduction pathways

A method for identifying compounds capable of inducing immunosuppression by inhibiting the CD28 signal transduction pathway and T cell comprises exposing cultured T cells to one or more test compounds. The T cells are obtained from a T cell line which stably incorporates DNA sequence comprising in reading frame an enhancer region responsive to a CD28-regulated nuclear binding protein and a marker gene. The cells are cultured under conditions which result in activation of both the T cell receptor and the CD28 receptor, resulting in enhanced expression of the marker gene. Test compounds which inhibit expression of the marker gene are considered as candidates for immunosuppressive drugs.

Screening assay for the identification ov novel immunosuppressives using

Chimeric proteins and DNA sequence encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA sequences may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.

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Mill Valley, CA, United States of America

Arthur Weiss