A YEAST SURFACE DISPLAY SYSTEM FOR THE DISCOVERY OF LIGANDS THAT TRIGGER CELL ACTIVATION

Opposing cells often communicate signalling events using multivalent i nteractions between receptors present on their cell surface. For examp le, T cells are typically activated when the T cell receptor (TCR) and its associated costimulatory molecules are multivalently engaged by t he appropriate ligands present on an antigen presenting cell. In this report, yeast expressing high cell-surface levels of a TCR ligand (a r ecombinant antibody to the TCR V beta domain) were shown to act as 'ps eudo' antigen presenting cells and induce T cell activation as monitor ed by increased levels of CD25 and CD69 and by downregulation of cell surface TCR. Similar levels of T cell activation could occur even when a 30-fold excess of irrelevant yeast was present, suggesting that suc h a yeast display system, by virtue of its ability to present ligands multivalently, may be used in highly sensitive procedures to identify novel polypeptides that interact multivalently with cell surface recep tors and thereby trigger specific cellular responses. (C) 1998 Elsevie r Science B.V. All rights reserved.